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2026,33(3):225-232, DOI: 10.3872/j.issn.1007-385X.2026.03.001
Abstract:
[Abstract] Dendritic cells (DCs), as the core initiators and regulators of anti-tumor immune responses, have emerged as important targets in tumor immunotherapy. Immunotherapeutic strategies targeting DCs, such as DC vaccines, have shown unique advantages in anti-tumor treatment. However, several challenges remain, including insufficient antigen presentation efficiency, resistance from the immunosuppressive microenvironment, and difficulties in achieving specific functional modulation. DCs in the tumor microenvironment (TME) exhibit high heterogeneity, and different DC subpopulations show complex diversity in differentiation and development, immune regulation, and effector outcomes. Elucidating the precise phenotypes and functional mechanisms of DC subpopulations is therefore crucial for developing novel DC-targeted immunotherapeutic strategies. In the TME, recruited conventional DCs, plasmacytoid DCs, and monocyte-derived DCs can interact with tumor-infiltrating immune cells and non-immune cells within the TME (including tumor cells, fibroblasts, endothelial cells, etc.) to activate anti-tumor immune responses. However, the TME can suppress DC recruitment and antigen-presenting capabilities through various means, including transcriptional regulation, epigenetic regulation, and metabolic reprogramming, and may even induce their transformation into tolerogenic DCs. Notably, newly discovered mature DCs enriched with immunoregulatory molecules exhibit bidirectional immunoregulatory functions, yet their origins and immune regulatory networks require in-depth research. With the development of single-cell technology and spatial omics, researchers can systematically analyze the functional diversity of DC subpopulations and their spatiotemporal interactions with the TME at single-cell resolution. These approaches are expected to provide new targets and insights for the development of next-generation precision immunotherapeutic strategies.[Key words] tumor microenvironment; dendritic cell subset; tumor; immunotherapy; immune checkpoint blockade therapy; cell-cell communication
[Abstract] Dendritic cells (DCs), as the core initiators and regulators of anti-tumor immune responses, have emerged as important targets in tumor immunotherapy. Immunotherapeutic strategies targeting DCs, such as DC vaccines, have shown unique advantages in anti-tumor treatment. However, several challenges remain, including insufficient antigen presentation efficiency, resistance from the immunosuppressive microenvironment, and difficulties in achieving specific functional modulation. DCs in the tumor microenvironment (TME) exhibit high heterogeneity, and different DC subpopulations show complex diversity in differentiation and development, immune regulation, and effector outcomes. Elucidating the precise phenotypes and functional mechanisms of DC subpopulations is therefore crucial for developing novel DC-targeted immunotherapeutic strategies. In the TME, recruited conventional DCs, plasmacytoid DCs, and monocyte-derived DCs can interact with tumor-infiltrating immune cells and non-immune cells within the TME (including tumor cells, fibroblasts, endothelial cells, etc.) to activate anti-tumor immune responses. However, the TME can suppress DC recruitment and antigen-presenting capabilities through various means, including transcriptional regulation, epigenetic regulation, and metabolic reprogramming, and may even induce their transformation into tolerogenic DCs. Notably, newly discovered mature DCs enriched with immunoregulatory molecules exhibit bidirectional immunoregulatory functions, yet their origins and immune regulatory networks require in-depth research. With the development of single-cell technology and spatial omics, researchers can systematically analyze the functional diversity of DC subpopulations and their spatiotemporal interactions with the TME at single-cell resolution. These approaches are expected to provide new targets and insights for the development of next-generation precision immunotherapeutic strategies.[Key words] tumor microenvironment; dendritic cell subset; tumor; immunotherapy; immune checkpoint blockade therapy; cell-cell communication
YANG Jianxun, ZHENG Rui, LIANG Sixin, PAN Jie, LI Yanlong, ZHAI Chenxi, ZHAO Xiaojuan, WANG Pengju, DONG Hao, YAN Bo, SUN Zhihong, ANG Angang
2026,33(3):233-242, DOI: 10.3872/j.issn.1007-385X.2026.03.002
Abstract:
[Abstract] Objective: To investigate whether ectopic expression of hemoglobin subunits (HBA/HBB) improves chimeric antigen receptor T cell (CAR-T cell) function and enhances cytotoxicity against tumor cells under hypoxic conditions. Methods: The CAR sequence targeting HER2 was synthesized by full gene synthesis technology, and the CAR lentiviral vectors co-expressing HBA or HBB were constructed. After packaging the lentivirus, human primary T lymphocytes were infected to prepare HBA CAR-T and HBB CAR-T. Hypoxia in mouse solid tumors was detected by hypoxia probes. The proportion of CAR-T cells in the tumor, the percentage of CAR-T cells expressing hemoglobin, and the levels of reactive oxygen species and apoptosis of CAR-T cells under different conditions were detected by flow cytometry. The expression of related hemoglobin subunits in CAR-T cells was detected by WB assay. The proliferation level of cells was detected by hemocytometer, the cytotoxicity of CAR-T cells against tumor cells was detected by luciferase reporter assay, the expression level of HIF-1α in CAR-T cells was detected by qPCR, the oxygen content in T cells was detected by MitoXpress Intra kit. Results: The solid tumor models constructed from different cell lines all exhibited significant hypoxia, and the infiltration level of CAR-T cells was significantly negatively correlated with the degree of hypoxia (P < 0.000 1). HBA CAR-T and HBB CAR-T were successfully constructed (positive rate > 60%), and the corresponding hemoglobin subunits were stably expressed. Under hypoxic conditions, the ROS level and apoptosis level of HBA CAR-T and HBB CAR-T significantly decreased, and their proliferation and cytotoxicity against tumor cells were significantly stronger than those of conventional CAR-T cells (all P < 0.05). HBA CAR-T and HBB CAR-T showed decreased HIF-1α expression (all P < 0.001), and their level of hypoxia significantly decreased (all P < 0.001). Conclusion: The ectopic expression of hemoglobin can reverse the functional impairment of CAR-T cells under hypoxic conditions and enhance their cytotoxicity against tumor cells in vitro.
[Abstract] Objective: To investigate whether ectopic expression of hemoglobin subunits (HBA/HBB) improves chimeric antigen receptor T cell (CAR-T cell) function and enhances cytotoxicity against tumor cells under hypoxic conditions. Methods: The CAR sequence targeting HER2 was synthesized by full gene synthesis technology, and the CAR lentiviral vectors co-expressing HBA or HBB were constructed. After packaging the lentivirus, human primary T lymphocytes were infected to prepare HBA CAR-T and HBB CAR-T. Hypoxia in mouse solid tumors was detected by hypoxia probes. The proportion of CAR-T cells in the tumor, the percentage of CAR-T cells expressing hemoglobin, and the levels of reactive oxygen species and apoptosis of CAR-T cells under different conditions were detected by flow cytometry. The expression of related hemoglobin subunits in CAR-T cells was detected by WB assay. The proliferation level of cells was detected by hemocytometer, the cytotoxicity of CAR-T cells against tumor cells was detected by luciferase reporter assay, the expression level of HIF-1α in CAR-T cells was detected by qPCR, the oxygen content in T cells was detected by MitoXpress Intra kit. Results: The solid tumor models constructed from different cell lines all exhibited significant hypoxia, and the infiltration level of CAR-T cells was significantly negatively correlated with the degree of hypoxia (P < 0.000 1). HBA CAR-T and HBB CAR-T were successfully constructed (positive rate > 60%), and the corresponding hemoglobin subunits were stably expressed. Under hypoxic conditions, the ROS level and apoptosis level of HBA CAR-T and HBB CAR-T significantly decreased, and their proliferation and cytotoxicity against tumor cells were significantly stronger than those of conventional CAR-T cells (all P < 0.05). HBA CAR-T and HBB CAR-T showed decreased HIF-1α expression (all P < 0.001), and their level of hypoxia significantly decreased (all P < 0.001). Conclusion: The ectopic expression of hemoglobin can reverse the functional impairment of CAR-T cells under hypoxic conditions and enhance their cytotoxicity against tumor cells in vitro.
2026,33(3):243-251, DOI: 10.3872/j.issn.1007-385X.2026.03.003
Abstract:
[Abstract] Objective: To investigate the mechanism by which actin-like protein 6A (ACTL6A) regulates ferroptosis and contributes to doxorubicin (DOX) resistance in diffuse large B cell lymphoma (DLBCL) cells. Methods: The parental DLBCL cell line SU-DHL-4 cells and its DOX-resistant variant SU-DHL-4/DOX cells were cultured. Changes in the expression of ACTL6A were detected by qPCR and WB assay. SU-DHL-4/DOX cells with ACTL6A knockdown were constructed by transfecting plasmids carrying a short hairpin RNA targeting ACTL6A (sh-ACTL6A) or its negative control (sh-NC). The expression levels of ACTL6A and ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase longchain family member 4 (ACSL4), were measured using qPCR and WB. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were performed to verify the targeting and regulatory relationship between ACTL6A and GPX4. SU-DHL-4/DOX cells were divided into Control, sh-NC, sh-ACTL6A, sh-NC + oe-GPX4, and sh-ACTL6A + oe-GPX4 groups. Corresponding plasmids were transfected into the cells. CCK-8 assay was used to detect cell survival rates of each group under different concentrations of DOX treatment. FerroOrange, Liperfluo, and DCFH-DA probes were used to detect ferrous ion (Fe2+) levels, lipid peroxidation, and reactive oxygen species (ROS) in each group of cells, respectively. A colorimetric method was used to measure the contents of glutathione (GSH) and malondialdehyde (MDA) in each group of cells. Results: Both ACTL6A mRNA and protein were highly expressed in SU-DHL-4/DOX cells (both P < 0.05), compared to SU-DHL-4 cells. ACTL6A and GPX4 have a targeting binding relationship. Knockdown of ACTL6A significantly decreased the mRNA and protein expression of ACTL6A and GPX4 in SU-DHL-4/DOX cells (both P < 0.05), indicating that ACTL6A regulates GPX4 expression. Knockdown of ACTL6A significantly inhibited the survival of SU-DHL-4/DOX cells, increased intracellular Fe2+, lipid peroxides, ROS, and MDA levels, and inhibited GSH production (all P < 0.05). However, overexpression of GPX4 in ACTL6A-knockdown cells upregulated the mRNA and protein expression levels of GPX4 in SU-DHL-4/DOX cells (both P < 0.05), increased cell survival rate, inhibited the production of intracellular Fe2+, lipid peroxides, ROS, and MDA, and increased GSH production (all P < 0.05). Conclusion: ACTL6A is highly expressed in DOX-resistant DLBCL cells. By regulating GPX4 expression, ACTL6A inhibits ferroptosis and promotes drug resistance in DLBCL cells.
[Abstract] Objective: To investigate the mechanism by which actin-like protein 6A (ACTL6A) regulates ferroptosis and contributes to doxorubicin (DOX) resistance in diffuse large B cell lymphoma (DLBCL) cells. Methods: The parental DLBCL cell line SU-DHL-4 cells and its DOX-resistant variant SU-DHL-4/DOX cells were cultured. Changes in the expression of ACTL6A were detected by qPCR and WB assay. SU-DHL-4/DOX cells with ACTL6A knockdown were constructed by transfecting plasmids carrying a short hairpin RNA targeting ACTL6A (sh-ACTL6A) or its negative control (sh-NC). The expression levels of ACTL6A and ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase longchain family member 4 (ACSL4), were measured using qPCR and WB. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were performed to verify the targeting and regulatory relationship between ACTL6A and GPX4. SU-DHL-4/DOX cells were divided into Control, sh-NC, sh-ACTL6A, sh-NC + oe-GPX4, and sh-ACTL6A + oe-GPX4 groups. Corresponding plasmids were transfected into the cells. CCK-8 assay was used to detect cell survival rates of each group under different concentrations of DOX treatment. FerroOrange, Liperfluo, and DCFH-DA probes were used to detect ferrous ion (Fe2+) levels, lipid peroxidation, and reactive oxygen species (ROS) in each group of cells, respectively. A colorimetric method was used to measure the contents of glutathione (GSH) and malondialdehyde (MDA) in each group of cells. Results: Both ACTL6A mRNA and protein were highly expressed in SU-DHL-4/DOX cells (both P < 0.05), compared to SU-DHL-4 cells. ACTL6A and GPX4 have a targeting binding relationship. Knockdown of ACTL6A significantly decreased the mRNA and protein expression of ACTL6A and GPX4 in SU-DHL-4/DOX cells (both P < 0.05), indicating that ACTL6A regulates GPX4 expression. Knockdown of ACTL6A significantly inhibited the survival of SU-DHL-4/DOX cells, increased intracellular Fe2+, lipid peroxides, ROS, and MDA levels, and inhibited GSH production (all P < 0.05). However, overexpression of GPX4 in ACTL6A-knockdown cells upregulated the mRNA and protein expression levels of GPX4 in SU-DHL-4/DOX cells (both P < 0.05), increased cell survival rate, inhibited the production of intracellular Fe2+, lipid peroxides, ROS, and MDA, and increased GSH production (all P < 0.05). Conclusion: ACTL6A is highly expressed in DOX-resistant DLBCL cells. By regulating GPX4 expression, ACTL6A inhibits ferroptosis and promotes drug resistance in DLBCL cells.
2026,33(3):252-261, DOI: 10.3872/j.issn.1007-385X.2026.03.004
Abstract:
[Abstract] Objective: To investigate the cytotoxic effects and underlying mechanisms of Bufalin (Buf) on ovarian cancer cells (A2780 and SKOV3) and to evaluate its synergistic cytotoxicity with cisplatin (DDP). Methods: A2780 and SKOV3 cells were routinely cultured. The effect of Buf on cell proliferation and its half-maximal inhibitory concentration (IC50) were determined using CCK-8 assay and colony formation assay. Following treatments with various concentrations of Buf, morphological changes of tumor cells were observed under a microscope, lactate dehydrogenase (LDH) release was measured using colorimetric assay, and the proportion of Annexin Ⅴ?PI? cells was analyzed using flow cytometry. The mRNA and protein expression levels of pyroptosis-related molecules were detected using qPCR and WB, respectively. Small interfering RNA was used to knock down gasdermin D (GSDMD) in A2780 and SKOV3 cells to validate its functional role. The synergistic cytotoxic effects of Buf and DDP against A2780 and SKOV3 cells were analyzed using the SynergyFinder platform, and the underlying mechanisms were further explored using flow cytometry, qPCR, and WB. Additionally, the synergistic effect of Buf and DDP on DDP-resistant A2780 and SKOV3 cells was evaluated using flow cytometry. Results: Compared with the control group, Buf significantly inhibited proliferation and migration of ovarian cancer cells (both P < 0.05), induced LDH release and cell pyroptosis (both P < 0.05), and upregulated the mRNA and protein expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), cysteine-aspartic acid protease 1 (CASP1), gasdermin D (GSDMD), interleukin(IL) -1β, and IL-18 (all P < 0.05). The combination of Buf and DDP synergistically inhibited the proliferation of A2780 and SKOV3 cells and further enhanced the sensitivity of DDP-resistant A2780 and SKOV3 cells to DDP. Conclusion: Buf induces pyroptosis in A2780 and SKOV3 cells by activating the NLRP3/CASP1/GSDMD signaling pathway and enhances the sensitivity of DDP-resistant A2780 and SKOV3 cells to DDP.
[Abstract] Objective: To investigate the cytotoxic effects and underlying mechanisms of Bufalin (Buf) on ovarian cancer cells (A2780 and SKOV3) and to evaluate its synergistic cytotoxicity with cisplatin (DDP). Methods: A2780 and SKOV3 cells were routinely cultured. The effect of Buf on cell proliferation and its half-maximal inhibitory concentration (IC50) were determined using CCK-8 assay and colony formation assay. Following treatments with various concentrations of Buf, morphological changes of tumor cells were observed under a microscope, lactate dehydrogenase (LDH) release was measured using colorimetric assay, and the proportion of Annexin Ⅴ?PI? cells was analyzed using flow cytometry. The mRNA and protein expression levels of pyroptosis-related molecules were detected using qPCR and WB, respectively. Small interfering RNA was used to knock down gasdermin D (GSDMD) in A2780 and SKOV3 cells to validate its functional role. The synergistic cytotoxic effects of Buf and DDP against A2780 and SKOV3 cells were analyzed using the SynergyFinder platform, and the underlying mechanisms were further explored using flow cytometry, qPCR, and WB. Additionally, the synergistic effect of Buf and DDP on DDP-resistant A2780 and SKOV3 cells was evaluated using flow cytometry. Results: Compared with the control group, Buf significantly inhibited proliferation and migration of ovarian cancer cells (both P < 0.05), induced LDH release and cell pyroptosis (both P < 0.05), and upregulated the mRNA and protein expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3), cysteine-aspartic acid protease 1 (CASP1), gasdermin D (GSDMD), interleukin(IL) -1β, and IL-18 (all P < 0.05). The combination of Buf and DDP synergistically inhibited the proliferation of A2780 and SKOV3 cells and further enhanced the sensitivity of DDP-resistant A2780 and SKOV3 cells to DDP. Conclusion: Buf induces pyroptosis in A2780 and SKOV3 cells by activating the NLRP3/CASP1/GSDMD signaling pathway and enhances the sensitivity of DDP-resistant A2780 and SKOV3 cells to DDP.
2026,33(3):262-269, DOI: 10.3872/j.issn.1007-385X.2026.03.005
Abstract:
[Abstract] Objective: To construct manganese porphyrin metal-organic framework nanoparticles (DPM) loaded with the STING agonist DMXAA, and to investigate their therapeutic effect against triple-negative breast cancer (TNBC) cells (4T1) and 4T1 cellmouse xenografts. Methods: DPM nanoparticles were prepared by physical adsorption. Their morphology and physicochemical properties were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and a nanoparticle size analyzer. 4T1 cells were cultured and divided into the following experimental groups: Control, Ultrasound Irradiation (US), DPM Treatment (DPM), and DPM Treatment combined with Ultrasound Irradiation (DPM + US). Cell viability was assessed using the CCK-8 assay. The expression of high mobility group box 1 (HMGB1) and calreticulin (CRT) was detected using immunofluorescence. Expression of STING pathway-related proteins was analyzed using WB. A 4T1 cell xenograft model was constructed and randomly divided into four groups. Following the treatments as those in the cell experiments, tumor volume was measured, and immunofluorescence was used to detect the expression of Ki-67, HMGB1, CRT, and hypoxia inducible factor-1ɑ (HIF-1α) in the transplanted tumor tissues. Additionally, TUNEL assay was used to detect cell apoptosis, flow cytometry was applied to assess immune cell activation, and H-E staining was used to evaluate the safety of the nanoparticles in major organs. Results: DPM exhibited a spindle shape with an average particle size of (268 ± 3.302) nm and a zeta potential of (33.1 ± 0.87) mV. In cell experiments, DPM combined with ultrasound irradiation significantly inhibited 4T1 cell growth (P < 0.001), elevated ROS levels (P < 0.001), induced upregulation of CRT expression (P < 0.001), and caused the translocation of HMGB1 from the nucleus to the cytoplasm. In addition, the STING signaling pathway was activated, as evidenced by significantly increased expression of p-STING, p-TBK1, and p-IRF3 proteins (all P < 0.001). In vivo, DPM combined with ultrasound irradiation significantly inhibited the growth of 4T1 cell xenograft (P < 0.001), promoted immune cell phenotypic transformation (P < 0.001), suppressed Ki-67 and HIF-1α expression in xenograft tissues, and reduced GSH production (P < 0.01). It also promoted CRT and HMGB1 protein expression and ROS production (P < 0.001). No significant effects on major organ structures were observed. Conclusion: DPM combined with ultrasound irradiation can significantly inhibit the growth of 4T1 cells and the xenografts through activation of the STING pathway, induce antitumor immune responses, and show no obvious toxicity to major organs.
[Abstract] Objective: To construct manganese porphyrin metal-organic framework nanoparticles (DPM) loaded with the STING agonist DMXAA, and to investigate their therapeutic effect against triple-negative breast cancer (TNBC) cells (4T1) and 4T1 cellmouse xenografts. Methods: DPM nanoparticles were prepared by physical adsorption. Their morphology and physicochemical properties were characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), and a nanoparticle size analyzer. 4T1 cells were cultured and divided into the following experimental groups: Control, Ultrasound Irradiation (US), DPM Treatment (DPM), and DPM Treatment combined with Ultrasound Irradiation (DPM + US). Cell viability was assessed using the CCK-8 assay. The expression of high mobility group box 1 (HMGB1) and calreticulin (CRT) was detected using immunofluorescence. Expression of STING pathway-related proteins was analyzed using WB. A 4T1 cell xenograft model was constructed and randomly divided into four groups. Following the treatments as those in the cell experiments, tumor volume was measured, and immunofluorescence was used to detect the expression of Ki-67, HMGB1, CRT, and hypoxia inducible factor-1ɑ (HIF-1α) in the transplanted tumor tissues. Additionally, TUNEL assay was used to detect cell apoptosis, flow cytometry was applied to assess immune cell activation, and H-E staining was used to evaluate the safety of the nanoparticles in major organs. Results: DPM exhibited a spindle shape with an average particle size of (268 ± 3.302) nm and a zeta potential of (33.1 ± 0.87) mV. In cell experiments, DPM combined with ultrasound irradiation significantly inhibited 4T1 cell growth (P < 0.001), elevated ROS levels (P < 0.001), induced upregulation of CRT expression (P < 0.001), and caused the translocation of HMGB1 from the nucleus to the cytoplasm. In addition, the STING signaling pathway was activated, as evidenced by significantly increased expression of p-STING, p-TBK1, and p-IRF3 proteins (all P < 0.001). In vivo, DPM combined with ultrasound irradiation significantly inhibited the growth of 4T1 cell xenograft (P < 0.001), promoted immune cell phenotypic transformation (P < 0.001), suppressed Ki-67 and HIF-1α expression in xenograft tissues, and reduced GSH production (P < 0.01). It also promoted CRT and HMGB1 protein expression and ROS production (P < 0.001). No significant effects on major organ structures were observed. Conclusion: DPM combined with ultrasound irradiation can significantly inhibit the growth of 4T1 cells and the xenografts through activation of the STING pathway, induce antitumor immune responses, and show no obvious toxicity to major organs.
2026,33(3):270-279, DOI: 10.3872/j.issn.1007-385X.2026.03.006
Abstract:
[Abstract] Objective: To investigate the molecular mechanisms by which Paris polyphyllaa saponin (PPⅡ) suppresses the malignant biological behaviors of thyroid cancer (TC). Methods: Thyroid cancer TPC1 cells were routinely cultured and divided into five experimental groups, designated as sh-NC, sh-lectin-galactoside binding-soluble 3 (sh-LGALS3), OE-NC, OE-LGALS3, and OELGALS3 + PPⅡ. TPC1 cells in each group were transfected with corresponding plasmids using transfection reagents.qPCR was used to detect the expression of LGALS3 mRNA in TPC1 cells. WB was performed to examine the expression of LGALS3 and PI3K/AKT signaling pathway-related proteins. CCK-8 assay, Transwell assay, wound healing assay, and flow cytometry were used to assess the proliferation, migration, invasion, and apoptosis of TPC1 cells in each group. Results: PPⅡ significantly inhibited the proliferation, migration, and invasion of TPC1 cells, while inducing apoptosis (all P < 0.000 1). Database analyses revealed that LGALS3 was highly expressed in thyroid cancer tissues (P < 0.001) and was identified as a potential target gene of PPⅡ. LGALS3 was highly expressed in TPC1 cells (P < 0.000 1). Knockdown of LGALS3 suppressed the malignant biological behaviors of TPC1 cells and promoted apoptosis (all P < 0.000 1). PPⅡ inhibited the malignant biological behaviors of TPC1 cells by downregulating LGALS3 mRNA and protein expression (P < 0.01 or P < 0.001). Furthermore, PP Ⅱ suppressed the activation of the PI3K/AKT signaling pathway by inhibiting LGALS3 expression (P < 0.001 or P < 0.000 1). LGALS3 promoted the malignant biological behaviors of TPC1 cells through the PI3K/AKT signaling pathway (P < 0.000 1). Conclusion: PPⅡ exerts anti-tumor effects in thyroid cancer by inhibiting LGALS3 expression in TPC1 cells and attenuating the overactivation of the PI3K/AKT signaling pathway.
[Abstract] Objective: To investigate the molecular mechanisms by which Paris polyphyllaa saponin (PPⅡ) suppresses the malignant biological behaviors of thyroid cancer (TC). Methods: Thyroid cancer TPC1 cells were routinely cultured and divided into five experimental groups, designated as sh-NC, sh-lectin-galactoside binding-soluble 3 (sh-LGALS3), OE-NC, OE-LGALS3, and OELGALS3 + PPⅡ. TPC1 cells in each group were transfected with corresponding plasmids using transfection reagents.qPCR was used to detect the expression of LGALS3 mRNA in TPC1 cells. WB was performed to examine the expression of LGALS3 and PI3K/AKT signaling pathway-related proteins. CCK-8 assay, Transwell assay, wound healing assay, and flow cytometry were used to assess the proliferation, migration, invasion, and apoptosis of TPC1 cells in each group. Results: PPⅡ significantly inhibited the proliferation, migration, and invasion of TPC1 cells, while inducing apoptosis (all P < 0.000 1). Database analyses revealed that LGALS3 was highly expressed in thyroid cancer tissues (P < 0.001) and was identified as a potential target gene of PPⅡ. LGALS3 was highly expressed in TPC1 cells (P < 0.000 1). Knockdown of LGALS3 suppressed the malignant biological behaviors of TPC1 cells and promoted apoptosis (all P < 0.000 1). PPⅡ inhibited the malignant biological behaviors of TPC1 cells by downregulating LGALS3 mRNA and protein expression (P < 0.01 or P < 0.001). Furthermore, PP Ⅱ suppressed the activation of the PI3K/AKT signaling pathway by inhibiting LGALS3 expression (P < 0.001 or P < 0.000 1). LGALS3 promoted the malignant biological behaviors of TPC1 cells through the PI3K/AKT signaling pathway (P < 0.000 1). Conclusion: PPⅡ exerts anti-tumor effects in thyroid cancer by inhibiting LGALS3 expression in TPC1 cells and attenuating the overactivation of the PI3K/AKT signaling pathway.
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Objective: To develop a chimeric costimulatory receptor targeting CD7 and prepare γδ T cells from healthy donors for the evaluation of its in vitro and in vivo cytotoxic effects against T-cell acute lymphoblastic leukemia (T-ALL) cells. Methods: γδ T cells expressing the CD7-targeting chimeric costimulatory receptor (CD7-DAP10-CCR-γδ T) were constructed. Using lentiviral transduction, the receptor was introduced into human peripheral blood-derived γδ T cells from healthy donors, followed by ex vivo expansion with artificial antigen-presenting cell (aAPC) expressing CD64, CD86, and CD137L. The cytotoxic activity of CD7-DAP10-CCR-γδ T cells against T-ALL cells (Jurkat), CD7-deficient Jurkat cells (CD7? Jurkat), and normal primary αβ T cells was assessed using the Annexin V/7-AAD assay. Furthermore, the in vivo efficacy was evaluated in an immunodeficient mouse model bearing T-ALL xenografts. Tumor burden was monitored regularly via in vivo imaging, and body weight changes and survival rates were recorded. Results: CD7-DAP10-CCR-γδ T cells were successfully expanded using aAPC, achieving an average expansion fold exceeding 10000. In vitro cytotoxicity assays demonstrated that these cells exhibited significantly high killing activity against T-ALL cells and Jurkat cells (P < 0.01), while showing limited cytotoxicity against CD7? Jurkat cells and negligible effects on normal primary CD7-high αβ T cells. In the T-ALL xenograft model, treatment with CD7-DAP10-CCR-γδ T cells resulted in a significant prolongation of survival compared to the PBS control group. Conclusion: This study establishes a robust aAPC-driven protocol for generating CD7-DAP10-CCR-γδ T cells with scalable expansion ( > 10 000-fold) and CD7-specific anti-tumor efficacy. The engineered cells exhibited selective cytotoxicity against T-ALL while sparing normal T cells, highlighting their therapeutic promise for relapsed/refractory T-ALL with mitigated on-target/off-tumor risks.
Objective: To develop a chimeric costimulatory receptor targeting CD7 and prepare γδ T cells from healthy donors for the evaluation of its in vitro and in vivo cytotoxic effects against T-cell acute lymphoblastic leukemia (T-ALL) cells. Methods: γδ T cells expressing the CD7-targeting chimeric costimulatory receptor (CD7-DAP10-CCR-γδ T) were constructed. Using lentiviral transduction, the receptor was introduced into human peripheral blood-derived γδ T cells from healthy donors, followed by ex vivo expansion with artificial antigen-presenting cell (aAPC) expressing CD64, CD86, and CD137L. The cytotoxic activity of CD7-DAP10-CCR-γδ T cells against T-ALL cells (Jurkat), CD7-deficient Jurkat cells (CD7? Jurkat), and normal primary αβ T cells was assessed using the Annexin V/7-AAD assay. Furthermore, the in vivo efficacy was evaluated in an immunodeficient mouse model bearing T-ALL xenografts. Tumor burden was monitored regularly via in vivo imaging, and body weight changes and survival rates were recorded. Results: CD7-DAP10-CCR-γδ T cells were successfully expanded using aAPC, achieving an average expansion fold exceeding 10000. In vitro cytotoxicity assays demonstrated that these cells exhibited significantly high killing activity against T-ALL cells and Jurkat cells (P < 0.01), while showing limited cytotoxicity against CD7? Jurkat cells and negligible effects on normal primary CD7-high αβ T cells. In the T-ALL xenograft model, treatment with CD7-DAP10-CCR-γδ T cells resulted in a significant prolongation of survival compared to the PBS control group. Conclusion: This study establishes a robust aAPC-driven protocol for generating CD7-DAP10-CCR-γδ T cells with scalable expansion ( > 10 000-fold) and CD7-specific anti-tumor efficacy. The engineered cells exhibited selective cytotoxicity against T-ALL while sparing normal T cells, highlighting their therapeutic promise for relapsed/refractory T-ALL with mitigated on-target/off-tumor risks.
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2012,19(5):550-555, DOI: 10.3872/j.issn.1007-385X.2012.5.018
Abstract:
骨髓增生异常综合征（myelodysplastic syndrome，MDS）的发病机制涉及多阶段、多因素，基因改变与表观遗传修饰可能共同参与了这一过程。DNA甲基化是表观遗传学中一种最为重要的修饰，MDS患者常表现为总体DNA高甲基化。使用DNA甲基转移酶（DNA methyltransferase，DNMT）抑制剂降低总体甲基化水平，在MDS患者中取得了富有成效的临床反应及血液学改善。DNMT抑制剂可分为两类：5-氮杂胞苷(5-azacytidine, 5-Aza-CdR)、地西他滨（5-Aza-2-deoxycytidine, decitabine）等核苷和核苷衍生物类抑制剂，它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善，但缓解率、疗效尚不够令人满意；肼苯哒嗪等非核苷类抑制剂。非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功，为MDS去甲基化治疗药物的研究开启了一种新思路。
骨髓增生异常综合征（myelodysplastic syndrome，MDS）的发病机制涉及多阶段、多因素，基因改变与表观遗传修饰可能共同参与了这一过程。DNA甲基化是表观遗传学中一种最为重要的修饰，MDS患者常表现为总体DNA高甲基化。使用DNA甲基转移酶（DNA methyltransferase，DNMT）抑制剂降低总体甲基化水平，在MDS患者中取得了富有成效的临床反应及血液学改善。DNMT抑制剂可分为两类：5-氮杂胞苷(5-azacytidine, 5-Aza-CdR)、地西他滨（5-Aza-2-deoxycytidine, decitabine）等核苷和核苷衍生物类抑制剂，它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善，但缓解率、疗效尚不够令人满意；肼苯哒嗪等非核苷类抑制剂。非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功，为MDS去甲基化治疗药物的研究开启了一种新思路。
2016,23(2):149-160, DOI: 10.3872/j.issn.1007-385X.2016.02.001
Abstract:
Immunocyte therapy for tumor has drawn a great attention in recent years due to its significant effect. Immunocytes, including T cell, NK cell and DCs, play a key role in immune responses of anti-tumors and immunotherapy of tumors. Among them, the techique of chimeric antigen receptor (CAR) modified-T cell (CAR-T) and inhibitor therapy which reverses CTLA-4 and PD-1/PD-L1 and so on immune checkpoints of tumor immune suppressive function have respectively achieved exciting results in therapies of blood tumors, melanoma and other solid tumors. How to further improve the efficacy, to increase adaptive tumor diseases and to control immune related adverse reactions of the therapy could become the focus of future research. NK cell will also take advantages of CAR technique and inhibitors of immune checkpoints to further strengthen its role in the tumor therapy. How to enhance the curative effect of DCs as the first therapeutic tumor vaccine approved by FDA based on its confirmed safe and non-toxic side effects could become a hot point. In this paper, problems that need to be solved in the field were further analyzed and prospected with combination of recent advances in the immunocyte-therapy for tumor.
Immunocyte therapy for tumor has drawn a great attention in recent years due to its significant effect. Immunocytes, including T cell, NK cell and DCs, play a key role in immune responses of anti-tumors and immunotherapy of tumors. Among them, the techique of chimeric antigen receptor (CAR) modified-T cell (CAR-T) and inhibitor therapy which reverses CTLA-4 and PD-1/PD-L1 and so on immune checkpoints of tumor immune suppressive function have respectively achieved exciting results in therapies of blood tumors, melanoma and other solid tumors. How to further improve the efficacy, to increase adaptive tumor diseases and to control immune related adverse reactions of the therapy could become the focus of future research. NK cell will also take advantages of CAR technique and inhibitors of immune checkpoints to further strengthen its role in the tumor therapy. How to enhance the curative effect of DCs as the first therapeutic tumor vaccine approved by FDA based on its confirmed safe and non-toxic side effects could become a hot point. In this paper, problems that need to be solved in the field were further analyzed and prospected with combination of recent advances in the immunocyte-therapy for tumor.
2018,25(1):23-27, DOI: 10.3872/j.issn.1007-385X.2018.01.004
Abstract:
Prostate cancer has become one of the most common malignant diseases in Chinese male. Hormonal therapy is an important and effective way to treat prostate cancer (especially advanced prostate cancer); however, some disputes merged from the clinical application are still to be solved. It seems crucial to unify the understanding and implement overall management to get satisfied effect in hormonal therapy of prostate cancer. According to guidelines and clinical trials in both domestic and overseas, we make a summary of series of problems that appeared in hormonal therapy of prostate cancer, such as treatment opportunity, treatment strategy, patients choose, prognosis and follow-up etc.
Prostate cancer has become one of the most common malignant diseases in Chinese male. Hormonal therapy is an important and effective way to treat prostate cancer (especially advanced prostate cancer); however, some disputes merged from the clinical application are still to be solved. It seems crucial to unify the understanding and implement overall management to get satisfied effect in hormonal therapy of prostate cancer. According to guidelines and clinical trials in both domestic and overseas, we make a summary of series of problems that appeared in hormonal therapy of prostate cancer, such as treatment opportunity, treatment strategy, patients choose, prognosis and follow-up etc.
2010,17(1):57-61, DOI: 10.3872/j.issn.1007-385X.2010.1.011
Abstract:
Objective: To prepare poly DL lactide poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase 1 (TIMP 1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods:The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP 1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP 1 mRNA in HepG2 cells was examined by semi quantitative RT PCR, and the proliferation of HepG2 cells was detected by MTT assay. Results:The microsphere encapsulating recombinant TIMP 1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×108/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP 1 PELA microsphere efficiently induced TIMP 1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion:PELA microsphere encapsulating recombinant TIMP 1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.
Objective: To prepare poly DL lactide poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase 1 (TIMP 1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods:The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP 1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP 1 mRNA in HepG2 cells was examined by semi quantitative RT PCR, and the proliferation of HepG2 cells was detected by MTT assay. Results:The microsphere encapsulating recombinant TIMP 1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×108/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP 1 PELA microsphere efficiently induced TIMP 1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion:PELA microsphere encapsulating recombinant TIMP 1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.
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Chinese Journal Of Cancer Biotheray ® 2026 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2026 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.