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Volume 32,Issue 9,2025 Table of Contents
2025, 32(9):899-905.
DOI: 10.3872/j.issn.1007-385X.2025.09.001
Abstract:
[Abstract] Adoptive cell therapy continues to drive innovation in cancer immunotherapy. Among the emerging approaches, bispecific antibody (BsAb)-armed T cell and NK cell (T/NK cell) technology leverages antibodies to specifically target tumor antigens and bridge immune effector cells, thereby endowing these cells with precise tumor-killing capabilities while overcoming the limitations of traditional therapeutic strategies. This technology is characterized by its high degree of standardization, controllable safety, and a short clinical translational cycle, demonstrating promising therapeutic potential in both solid tumors and hematologic malignancies. This article provides a comprehensive review of the advancements in chimeric antigen receptor-engineered T/NK cell (CAR-T/NK cell), tumor-infiltrating lymphocyte (TIL), and cytokine-induced memory-like NK cell (CIML NK) therapies. Particular emphasis is placed on the mechanisms of action, advantages, clinical progress, and emerging trends of BsAb-armed T/NK cell therapy.
[Abstract] Adoptive cell therapy continues to drive innovation in cancer immunotherapy. Among the emerging approaches, bispecific antibody (BsAb)-armed T cell and NK cell (T/NK cell) technology leverages antibodies to specifically target tumor antigens and bridge immune effector cells, thereby endowing these cells with precise tumor-killing capabilities while overcoming the limitations of traditional therapeutic strategies. This technology is characterized by its high degree of standardization, controllable safety, and a short clinical translational cycle, demonstrating promising therapeutic potential in both solid tumors and hematologic malignancies. This article provides a comprehensive review of the advancements in chimeric antigen receptor-engineered T/NK cell (CAR-T/NK cell), tumor-infiltrating lymphocyte (TIL), and cytokine-induced memory-like NK cell (CIML NK) therapies. Particular emphasis is placed on the mechanisms of action, advantages, clinical progress, and emerging trends of BsAb-armed T/NK cell therapy.
2025, 32(9):906-911.
DOI: 10.3872/j.issn.1007-385X.2025.09.002
Abstract:
[Abstract] Objective: To investigate the regulatory role of phosphoglycerate mutase 1 (PGAM1) in lung cancer LLC cell proliferation and migration, and to explore its impact on the function and infiltration of CD8? T cells within the tumor microenvironment. Methods: LLC cells were infected with shPGAM1 and shNC lentiviruses, and stable cell lines were established and designated as the shPGAM1 group and the NC group, respectively. WB and qPCR were used to assess the protein and mRNA expression levels of PGAM1 in both groups. Cell proliferation and migration after PGAM1 knockdown were assessed using the CCK-8 assay and real-time cell analyzer. Flow cytometry was employed to detect the expression of CD8? T-cell functional receptors (TIM-3, PD-1, GrzmB, Ki67) after co culture with cells from each group in vitro. A subcutaneous LLC xenograft model was established in mice to examine the effect of PGAM1 on tumor growth, and flow cytometry was used to evaluate the impact of PGAM1 knockdown on CD8? T cell infiltration in the tumor microenvironment. Results: The protein and mRNA expression levels of PGAM1 were significantly reduced in the shPGAM1 group compared with the NC group. Knockdown of PGAM1 significantly reduced the proliferation and migration of LLC cells (P < 0.000 1 or P < 0.05). After co-culture with shPGAM1 cells, the expression of exhaustion markers (TIM-3, PD-1) on CD8? T cells decreased notably (P < 0.000 1 or P < 0.01). Knockdown of PGAM1 significantly inhibited tumor growth and increased CD8? T cell infiltration in tumor tissues (P < 0.000 1). Conclusion: Targeted knockdown of PGAM1 inhibits tumor cell proliferation and migration, reduces the expression of exhaustion markers on CD8? T cells, and enhances T cell infiltration within tumors, thereby exerting dual effects on tumor growth and antitumor immunity.
[Abstract] Objective: To investigate the regulatory role of phosphoglycerate mutase 1 (PGAM1) in lung cancer LLC cell proliferation and migration, and to explore its impact on the function and infiltration of CD8? T cells within the tumor microenvironment. Methods: LLC cells were infected with shPGAM1 and shNC lentiviruses, and stable cell lines were established and designated as the shPGAM1 group and the NC group, respectively. WB and qPCR were used to assess the protein and mRNA expression levels of PGAM1 in both groups. Cell proliferation and migration after PGAM1 knockdown were assessed using the CCK-8 assay and real-time cell analyzer. Flow cytometry was employed to detect the expression of CD8? T-cell functional receptors (TIM-3, PD-1, GrzmB, Ki67) after co culture with cells from each group in vitro. A subcutaneous LLC xenograft model was established in mice to examine the effect of PGAM1 on tumor growth, and flow cytometry was used to evaluate the impact of PGAM1 knockdown on CD8? T cell infiltration in the tumor microenvironment. Results: The protein and mRNA expression levels of PGAM1 were significantly reduced in the shPGAM1 group compared with the NC group. Knockdown of PGAM1 significantly reduced the proliferation and migration of LLC cells (P < 0.000 1 or P < 0.05). After co-culture with shPGAM1 cells, the expression of exhaustion markers (TIM-3, PD-1) on CD8? T cells decreased notably (P < 0.000 1 or P < 0.01). Knockdown of PGAM1 significantly inhibited tumor growth and increased CD8? T cell infiltration in tumor tissues (P < 0.000 1). Conclusion: Targeted knockdown of PGAM1 inhibits tumor cell proliferation and migration, reduces the expression of exhaustion markers on CD8? T cells, and enhances T cell infiltration within tumors, thereby exerting dual effects on tumor growth and antitumor immunity.
2025, 32(9):912-919.
DOI: 10.3872/j.issn.1007-385X.2025.09.003
Abstract:
[Abstract] Objective: To investigate the effects of long intergenic non-coding RNA00894 (LINC00894) on the malignant biological behaviors of gastric cancer (GC) cells via regulating the microRNA-205-5p (miR-205-5p)/glycoprotein non-metastatic melanoma protein B (GPNMB) axis. Methods: Twenty-five pairs of gastric cancer tissues and corresponding adjacent tissues were collected from patients undergoing surgical resection at the First Hospital of Hebei Medical University between November 2022 and September 2023. BGC823 cells were routinely cultured and into control, sh-NC, sh-LINC00894, sh-LINC00894 + anti-NC, and sh-LINC00894+anti miR-205-5p groups, followed by corresponding plasmids transfection using transfection reagents. The mRNA expression of LINC00894, miR-205-5p, and GPNMB in BGC823 cells and cancer tissues of each group was detected using qPCR. Dual luciferase reporter gene assay and AGO2-RNA immunoprecipitation were used to verify the targeted binding relationships between LINC00894 and miR-205-5p, as well as between miR-205-5p and GPNMB. Colony formation assay, EdU staining, wound-healing assay, and Transwell assay were performed to detect cell proliferation, migration and invasion abilities. Western blotting was used to detect the protein expression of CDK1, MMP-2 and MMP-9 in each group of cells. A nude mouse xenograft model was established to determine the effect of LINC00894 knockdown on tumor growth, and immunohistochemistry was used to detect the protein expression of GPNMB in xenograft tissues. Results: LINC00894 and GPNMB were significantly upregulated in gastric cancer tissues and cells,while miR-205-5p was downregulated (both P < 0.05). LINC00894 negatively regulated miR-205-5p, while miR-205-5p negatively regulated GPNMB (all P < 0.05). Knocking down LINC00894 promoted miR-205-5p expression and inhibited GPNMB expression in BGC823 cells (all P < 0.05). Additionally, LINC00894 knockdown suppressed the proliferation, migration and invasion abilities of BGC823 cells, as well as the protein expression of CDK1, MMP-2, and MMP-9 (all P < 0.05). Inhibition of miR-205-5p reversed these effects (all P < 0.05). Knocking down LINC00894 inhibited the growth of BGC823 cell-transplanted tumors, promoted miR-205-5p expression, and inhibited GPNMB protein expression (all P < 0.05). Conclusion: LINC00894 is highly expressed in gastric cancer tissues and cells, while miR-205-5p is downregulated. Knockdown of LINC00894 can regulate the expression of miR-205-5p/GPNMB pathway-related proteins in BGC823 cells, thereby inhibiting their malignant biological behaviors.
[Abstract] Objective: To investigate the effects of long intergenic non-coding RNA00894 (LINC00894) on the malignant biological behaviors of gastric cancer (GC) cells via regulating the microRNA-205-5p (miR-205-5p)/glycoprotein non-metastatic melanoma protein B (GPNMB) axis. Methods: Twenty-five pairs of gastric cancer tissues and corresponding adjacent tissues were collected from patients undergoing surgical resection at the First Hospital of Hebei Medical University between November 2022 and September 2023. BGC823 cells were routinely cultured and into control, sh-NC, sh-LINC00894, sh-LINC00894 + anti-NC, and sh-LINC00894+anti miR-205-5p groups, followed by corresponding plasmids transfection using transfection reagents. The mRNA expression of LINC00894, miR-205-5p, and GPNMB in BGC823 cells and cancer tissues of each group was detected using qPCR. Dual luciferase reporter gene assay and AGO2-RNA immunoprecipitation were used to verify the targeted binding relationships between LINC00894 and miR-205-5p, as well as between miR-205-5p and GPNMB. Colony formation assay, EdU staining, wound-healing assay, and Transwell assay were performed to detect cell proliferation, migration and invasion abilities. Western blotting was used to detect the protein expression of CDK1, MMP-2 and MMP-9 in each group of cells. A nude mouse xenograft model was established to determine the effect of LINC00894 knockdown on tumor growth, and immunohistochemistry was used to detect the protein expression of GPNMB in xenograft tissues. Results: LINC00894 and GPNMB were significantly upregulated in gastric cancer tissues and cells,while miR-205-5p was downregulated (both P < 0.05). LINC00894 negatively regulated miR-205-5p, while miR-205-5p negatively regulated GPNMB (all P < 0.05). Knocking down LINC00894 promoted miR-205-5p expression and inhibited GPNMB expression in BGC823 cells (all P < 0.05). Additionally, LINC00894 knockdown suppressed the proliferation, migration and invasion abilities of BGC823 cells, as well as the protein expression of CDK1, MMP-2, and MMP-9 (all P < 0.05). Inhibition of miR-205-5p reversed these effects (all P < 0.05). Knocking down LINC00894 inhibited the growth of BGC823 cell-transplanted tumors, promoted miR-205-5p expression, and inhibited GPNMB protein expression (all P < 0.05). Conclusion: LINC00894 is highly expressed in gastric cancer tissues and cells, while miR-205-5p is downregulated. Knockdown of LINC00894 can regulate the expression of miR-205-5p/GPNMB pathway-related proteins in BGC823 cells, thereby inhibiting their malignant biological behaviors.
2025, 32(9):920-926.
DOI: 10.3872/j.issn.1007-385X.2025.09.004
Abstract:
[Abstract] Objective: To investigate the effects of long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) on the malignant biological behavior of hepatocellular carcinoma (HCC) cells by targeting miR-579-3p/secreted protein acidic and rich in cysteine (SPARC) axis. Methods: Normal human hepatocytes (LO2) and HCC cells (Huh7, Hep3B, HepG2) were routinely cultured. Huh7 cells were randomly divided into control, sh-NC, sh-SNHG14, sh-SNHG14 + anti-NC, and sh-SNHG14 + anti-miR-579-3p groups. The mRNA expression levels of SNHG14, miR-579-3p, and SPARC in the above cells were detected by qPCR. Dual-luciferase reporter gene assay was applied to verify the regulatory relationship between SNHG14 and miR-579-3p, as well as between miR-579 3p and SPARC. The proliferation, migration, invasion, and apoptosis of Huh7 cells in each group were assessed using MTT, wound healing, Transwell, and flow cytometry assays, respectively. WB was used to detect the protein levels of PCNA, E-cadherin, vimentin, and SPARC. Results: In HCC cells, SNHG14 and SPARC mRNA were upregulated, whereas miR-579-3p was downregulated (all P < 0.05). There was a direct binding regulatory relationship between SNHG14 and miR-579-3p, as well as between miR-579-3p and SPARC mRNA (all P < 0.05). Knockdown of SNHG14 significantly inhibited the proliferation, migration, invasion, and the expression of PCNA and vimentin, as well as the mRNA and protein expression of SPARC in Huh7 cells (all P < 0.05), while promoting apoptosis, expression of miR-579-3p, and E-cadherin expression (all P < 0.05). Inhibition of miR-579-3p partially reversed the effects of SNHG14 knockdown on Huh7 cells (all P < 0.05). Conclusion: Knockdown of SNHG14 can inhibit the malignant biological behaviors of Huh7 cells and promote their apoptosis by targeting the miR-579-3p/SPARC axis. The SNHG14/miR-579-3p/SPARC axis may represent a potential therapeutic target for HCC.
[Abstract] Objective: To investigate the effects of long non-coding RNA (lncRNA) small nucleolar RNA host gene 14 (SNHG14) on the malignant biological behavior of hepatocellular carcinoma (HCC) cells by targeting miR-579-3p/secreted protein acidic and rich in cysteine (SPARC) axis. Methods: Normal human hepatocytes (LO2) and HCC cells (Huh7, Hep3B, HepG2) were routinely cultured. Huh7 cells were randomly divided into control, sh-NC, sh-SNHG14, sh-SNHG14 + anti-NC, and sh-SNHG14 + anti-miR-579-3p groups. The mRNA expression levels of SNHG14, miR-579-3p, and SPARC in the above cells were detected by qPCR. Dual-luciferase reporter gene assay was applied to verify the regulatory relationship between SNHG14 and miR-579-3p, as well as between miR-579 3p and SPARC. The proliferation, migration, invasion, and apoptosis of Huh7 cells in each group were assessed using MTT, wound healing, Transwell, and flow cytometry assays, respectively. WB was used to detect the protein levels of PCNA, E-cadherin, vimentin, and SPARC. Results: In HCC cells, SNHG14 and SPARC mRNA were upregulated, whereas miR-579-3p was downregulated (all P < 0.05). There was a direct binding regulatory relationship between SNHG14 and miR-579-3p, as well as between miR-579-3p and SPARC mRNA (all P < 0.05). Knockdown of SNHG14 significantly inhibited the proliferation, migration, invasion, and the expression of PCNA and vimentin, as well as the mRNA and protein expression of SPARC in Huh7 cells (all P < 0.05), while promoting apoptosis, expression of miR-579-3p, and E-cadherin expression (all P < 0.05). Inhibition of miR-579-3p partially reversed the effects of SNHG14 knockdown on Huh7 cells (all P < 0.05). Conclusion: Knockdown of SNHG14 can inhibit the malignant biological behaviors of Huh7 cells and promote their apoptosis by targeting the miR-579-3p/SPARC axis. The SNHG14/miR-579-3p/SPARC axis may represent a potential therapeutic target for HCC.
5 Mechanistic role and clinical potential of POLD1 in bladder cancer cell proliferation and migration
2025, 32(9):927-933.
DOI: 10.3872/j.issn.1007-385X.2025.09.005
Abstract:
[Abstract] Objective: To investigate the expression of DNA polymerase δ catalytic subunit gene 1 (POLD1) in bladder cancer tissues and its correlation with patients’ clinicopathological characteristics and prognosis, and to explore its effect on the proliferation, migration, and invasion of bladder cancer 5637 cells. Methods: Sixty cases of bladder cancer tissues and paired adjacent noncancerous tissues preserved in the Department of Pathology, Shanxi Bethune Hospital, from January to June 2021 were collected. Immunohistochemistry was performed to detect POLD1 protein expression in bladder cancer tissues. Patients were divided into high- and low-expression groups according to POLD1 levels, and the correlations between POLD1 level with clinicopathological characteristics and prognosis were analyzed. Bladder cancer 5637 cells were cultured routinely and divided into a control group (untransfected), a sh-NC group (transfected with sh-NC-GFP lentivirus vector), and a sh-POLD1 group (transfected with sh-POLD1 GFP lentiviral vector). Transfection efficiency was validated using fluorescence microscopy and WB method. Cell proliferation, migration, and invasion were assessed using CCK-8, wound-healing, and Transwell assays. 5637 cell-transplanted tumor experiment was performed to detect the effect of POLD1 knockdown on the growth of transplanted tumors. Results: POLD1 was highly expressed in bladder cancer tissues (P < 0.05). High POLD1 expression was significantly associated with advanced clinical stage and pathological grade (all P < 0.05). Patients with high POLD1 expression exhibited shorter progression-free survival, reduced overall survival, lower 3 year survival rate, and higher recurrence and metastasis rate (all P < 0.05). The expression of POLD1 was successfully knocked down in 5637 cells, which significantly inhibited the proliferation, migration, and invasion abilities of 5637 cells (all P < 0.05). In vivo, POLD1 knockdown significantly inhibited the growth of transplanted tumors (P < 0.05). Conclusion: POLD1 is highly expressed in bladder cancer tissues, and its upregulation is associated with tumor stage, pathological grade, and patient prognosis. POLD1 knockdown can inhibit the malignant biological behaviors of bladder cancer cells.
[Abstract] Objective: To investigate the expression of DNA polymerase δ catalytic subunit gene 1 (POLD1) in bladder cancer tissues and its correlation with patients’ clinicopathological characteristics and prognosis, and to explore its effect on the proliferation, migration, and invasion of bladder cancer 5637 cells. Methods: Sixty cases of bladder cancer tissues and paired adjacent noncancerous tissues preserved in the Department of Pathology, Shanxi Bethune Hospital, from January to June 2021 were collected. Immunohistochemistry was performed to detect POLD1 protein expression in bladder cancer tissues. Patients were divided into high- and low-expression groups according to POLD1 levels, and the correlations between POLD1 level with clinicopathological characteristics and prognosis were analyzed. Bladder cancer 5637 cells were cultured routinely and divided into a control group (untransfected), a sh-NC group (transfected with sh-NC-GFP lentivirus vector), and a sh-POLD1 group (transfected with sh-POLD1 GFP lentiviral vector). Transfection efficiency was validated using fluorescence microscopy and WB method. Cell proliferation, migration, and invasion were assessed using CCK-8, wound-healing, and Transwell assays. 5637 cell-transplanted tumor experiment was performed to detect the effect of POLD1 knockdown on the growth of transplanted tumors. Results: POLD1 was highly expressed in bladder cancer tissues (P < 0.05). High POLD1 expression was significantly associated with advanced clinical stage and pathological grade (all P < 0.05). Patients with high POLD1 expression exhibited shorter progression-free survival, reduced overall survival, lower 3 year survival rate, and higher recurrence and metastasis rate (all P < 0.05). The expression of POLD1 was successfully knocked down in 5637 cells, which significantly inhibited the proliferation, migration, and invasion abilities of 5637 cells (all P < 0.05). In vivo, POLD1 knockdown significantly inhibited the growth of transplanted tumors (P < 0.05). Conclusion: POLD1 is highly expressed in bladder cancer tissues, and its upregulation is associated with tumor stage, pathological grade, and patient prognosis. POLD1 knockdown can inhibit the malignant biological behaviors of bladder cancer cells.
2025, 32(9):934-940.
DOI: 10.3872/j.issn.1007-385X.2025.09.006
Abstract:
[Abstract] Objective: To investigate the effects of echinatin (Ech) on the malignant biological behavior and immune escape of lung cancer A549 cells and its underlying mechanisms. Methods: Normal lung epithelial cells (BEAS-2B) and A549 cells were routinely cultured and treated with different concentrations of Ech for 24h. Cell viability was assessed using the MTT assay, and concentrations of 20, 30, and 40 μmol/L were selected for subsequent experiments. A549 cells were divided into the following groups: control group (0 μmol/L Ech), low- (20 μmol/L), medium- (30 μmol/L), and high-concentration (40 μmol/L) Ech groups (Ech-L, Ech-M, Ech-H), and high-dose Ech combined with the pathway inhibitor H-151 (1.0 μmol/L) group (Ech-H + H-151). Cell proliferation, migration, and invasion were evaluated using the EdU assay, wound-healing assay, and Transwell assay, respectively. Western blotting (WB) assay was applied to detect the expression of proteins related to proliferation, migration, invasion, and the STING/TBK1/IRF3 signaling pathway. Subsequently, A549 cells were co-cultured with CD8+ T cells, and trypan blue staining was used to detect CD8+ T cell viability. The levels of type Ⅰ interferon (IFN-Ⅰ) in the co-culture supernatants were detected by WB, while the levels of programmed death ligand 1 (PD-L1), interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-β (TGF-β) were determined using ELISA. Results: Ech inhibited the viability of A549 cells in a dose-dependent manner (all P < 0.05) but had no significant effect on the viability of BEAS-2B cells. Ech dose-dependently inhibited the proliferation, migration and invasion of A549 cells (all P < 0.05), as well as the protein expression of cyclinD1, Ki67, MMP2, MMP9, STING, p-TBK1 and p-IRF3 (all P < 0.05). These effects were partially reversed by H-151. Ech dose-dependently promoted the survival of CD8+ T cells co-cultured with A549 cells (all P < 0.05), enhanced IFN-Ⅰ expression (all P < 0.05), and inhibited the secretion of PD-L1, IL-10, IL-4, and TGF-β (all P < 0.05), with H-151 partially reversing these effects (all P < 0.05). Conclusion: Ech inhibits malignant biological behavior and immune escape of lung cancer A549 cells by activating the STING/TBK1/IRF3 signaling pathway.
[Abstract] Objective: To investigate the effects of echinatin (Ech) on the malignant biological behavior and immune escape of lung cancer A549 cells and its underlying mechanisms. Methods: Normal lung epithelial cells (BEAS-2B) and A549 cells were routinely cultured and treated with different concentrations of Ech for 24h. Cell viability was assessed using the MTT assay, and concentrations of 20, 30, and 40 μmol/L were selected for subsequent experiments. A549 cells were divided into the following groups: control group (0 μmol/L Ech), low- (20 μmol/L), medium- (30 μmol/L), and high-concentration (40 μmol/L) Ech groups (Ech-L, Ech-M, Ech-H), and high-dose Ech combined with the pathway inhibitor H-151 (1.0 μmol/L) group (Ech-H + H-151). Cell proliferation, migration, and invasion were evaluated using the EdU assay, wound-healing assay, and Transwell assay, respectively. Western blotting (WB) assay was applied to detect the expression of proteins related to proliferation, migration, invasion, and the STING/TBK1/IRF3 signaling pathway. Subsequently, A549 cells were co-cultured with CD8+ T cells, and trypan blue staining was used to detect CD8+ T cell viability. The levels of type Ⅰ interferon (IFN-Ⅰ) in the co-culture supernatants were detected by WB, while the levels of programmed death ligand 1 (PD-L1), interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-β (TGF-β) were determined using ELISA. Results: Ech inhibited the viability of A549 cells in a dose-dependent manner (all P < 0.05) but had no significant effect on the viability of BEAS-2B cells. Ech dose-dependently inhibited the proliferation, migration and invasion of A549 cells (all P < 0.05), as well as the protein expression of cyclinD1, Ki67, MMP2, MMP9, STING, p-TBK1 and p-IRF3 (all P < 0.05). These effects were partially reversed by H-151. Ech dose-dependently promoted the survival of CD8+ T cells co-cultured with A549 cells (all P < 0.05), enhanced IFN-Ⅰ expression (all P < 0.05), and inhibited the secretion of PD-L1, IL-10, IL-4, and TGF-β (all P < 0.05), with H-151 partially reversing these effects (all P < 0.05). Conclusion: Ech inhibits malignant biological behavior and immune escape of lung cancer A549 cells by activating the STING/TBK1/IRF3 signaling pathway.
2025, 32(9):941-947.
DOI: 10.3872/j.issn.1007-385X.2025.09.007
Abstract:
[Abstract] Objective: To investigate the effects of formononetin on the malignant biological behavior and angiogenesis of gallbladder cancer GBC-SD cells through regulation of the JAK2/STAT3 signaling pathway. Methods: GBC-SD cells were cultured routinely, and their xenograft nude mouse models were constructed. The cells and mice were divided into control group, formononetin group, colivelin (JAK2/STAT3 activator) group, and formononetin + colivelin group. Cell proliferation, migration and invasion, and apoptosis were assessed using MTT, Transwell, and flow cytometry assays, respectively. ELISA was applied to measure the secretion levels of vascular endothelial growth factor (VEGF) in cells of each group. Vasculogenic mimicry (VM) formation assay was used to detect the tube formation ability of each group of cells. In vivo, the effects of formononetin on xenograft tumor growth were examined, and CD31 and VEGF expression in xenograft tissues were detected by immunohistochemistry. Western blotting was applied to analyze JAK2/ STAT3 phosphorylation levels in both cells and tumor tissues. Results: Formononetin significantly inhibited the proliferation, migration, and invasion of GBC-SD cells and promoted apoptosis (all P < 0.05). It also suppressed VEGF secretion and VM formation in GBC-SD cells (all P < 0.05), inhibited the growth and vascular formation of GBC-SD xenograft tumors (all P < 0.05), reduced VEGF expression in transplanted tumor tissues, and decreased phosphorylation of the JAK2/STAT3 pathway in both GBC-SD cells and their xenograft tissues. These effects of formononetin were partially reversed by colivelin (all P < 0.05). Conclusion: Formononetin inhibits GBC-SD cell proliferation, migration, invasion, and angiogenesis, and promotes apoptosis by suppressing the JAK2/STAT3 signaling pathway. The JAK2/STAT3 signaling pathway may serve as a potential therapeutic target for gallbladder cancer.
[Abstract] Objective: To investigate the effects of formononetin on the malignant biological behavior and angiogenesis of gallbladder cancer GBC-SD cells through regulation of the JAK2/STAT3 signaling pathway. Methods: GBC-SD cells were cultured routinely, and their xenograft nude mouse models were constructed. The cells and mice were divided into control group, formononetin group, colivelin (JAK2/STAT3 activator) group, and formononetin + colivelin group. Cell proliferation, migration and invasion, and apoptosis were assessed using MTT, Transwell, and flow cytometry assays, respectively. ELISA was applied to measure the secretion levels of vascular endothelial growth factor (VEGF) in cells of each group. Vasculogenic mimicry (VM) formation assay was used to detect the tube formation ability of each group of cells. In vivo, the effects of formononetin on xenograft tumor growth were examined, and CD31 and VEGF expression in xenograft tissues were detected by immunohistochemistry. Western blotting was applied to analyze JAK2/ STAT3 phosphorylation levels in both cells and tumor tissues. Results: Formononetin significantly inhibited the proliferation, migration, and invasion of GBC-SD cells and promoted apoptosis (all P < 0.05). It also suppressed VEGF secretion and VM formation in GBC-SD cells (all P < 0.05), inhibited the growth and vascular formation of GBC-SD xenograft tumors (all P < 0.05), reduced VEGF expression in transplanted tumor tissues, and decreased phosphorylation of the JAK2/STAT3 pathway in both GBC-SD cells and their xenograft tissues. These effects of formononetin were partially reversed by colivelin (all P < 0.05). Conclusion: Formononetin inhibits GBC-SD cell proliferation, migration, invasion, and angiogenesis, and promotes apoptosis by suppressing the JAK2/STAT3 signaling pathway. The JAK2/STAT3 signaling pathway may serve as a potential therapeutic target for gallbladder cancer.
2025, 32(9):948-956.
DOI: 10.3872/j.issn.1007-385X.2025.09.008
Abstract:
[Abstract] Objective: To construct a prognostic model across multiple cancer types based on exhausted T cell (Tex) gene sets and to identify novel Tex cell markers. Methods: A pan-cancer single-cell dataset of CD8+ T cells was utilized to identify the pan-cancer Tex gene set. Differential expression analysis and Cox regression analysis of TCGA data were performed to screen pan-cancer prognostic genes. These genes were then intersected with the Tex gene set, yielding a pan-cancer Tex prognostic gene set. Cox regression analysis was used to construct a pan-cancer prognostic model, and the model's performance was evaluated using Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve analyses. In addition, correlation analysis was further applied to explore the role of TNFRSF18 in immunotherapy. Results: Cox regression analysis identified CXCL13, CDKN2A, TNFRSF18, and IL2RA as key prognostic genes, on which the prognostic model was constructed. Survival analysis showed that patients in the low-risk group exhibited significantly higher survival rates across various cancer types (P < 0.05). Single-cell data analysis demonstrated that TNFRSF18 was specifically expressed in Tex cells and was significantly upregulated in tumor samples from various cancers (P < 0.05). Conclusion: The pan-cancer Tex cell-based prognostic model showed robust predictive performance across various cancers. TNFRSF18 may function as a novel potential biomarker of Tex cells and play a role in cancer immunotherapy.
[Abstract] Objective: To construct a prognostic model across multiple cancer types based on exhausted T cell (Tex) gene sets and to identify novel Tex cell markers. Methods: A pan-cancer single-cell dataset of CD8+ T cells was utilized to identify the pan-cancer Tex gene set. Differential expression analysis and Cox regression analysis of TCGA data were performed to screen pan-cancer prognostic genes. These genes were then intersected with the Tex gene set, yielding a pan-cancer Tex prognostic gene set. Cox regression analysis was used to construct a pan-cancer prognostic model, and the model's performance was evaluated using Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve analyses. In addition, correlation analysis was further applied to explore the role of TNFRSF18 in immunotherapy. Results: Cox regression analysis identified CXCL13, CDKN2A, TNFRSF18, and IL2RA as key prognostic genes, on which the prognostic model was constructed. Survival analysis showed that patients in the low-risk group exhibited significantly higher survival rates across various cancer types (P < 0.05). Single-cell data analysis demonstrated that TNFRSF18 was specifically expressed in Tex cells and was significantly upregulated in tumor samples from various cancers (P < 0.05). Conclusion: The pan-cancer Tex cell-based prognostic model showed robust predictive performance across various cancers. TNFRSF18 may function as a novel potential biomarker of Tex cells and play a role in cancer immunotherapy.
9 Experimental study on the effects of panobinostat on melanoma growth and immunogenicity mechanisms
2025, 32(9):957-967.
DOI: 10.3872/j.issn.1007-385X.2025.09.009
Abstract:
[Abstract] Objective: To investigate the effects of the histone deacetylase (HDAC) inhibitor panobinostat on melanoma growth, tumor immunity, and the underlying mechanisms. Methods: B16F0 melanoma cells were cultured and treated with different concentrations of panobinostat. The effect of panobinostat on HDAC expression in B16F0 cells was detected by WB. The effects of panobinostat on the proliferation, migration, invasion, apoptosis and cell cycle of B16F0 cells were detected by CCK-8 assay, wound-healing assay, Transwell assay and flow cytometry, respectively. The effect of panobinostat on gene expression in B16F0 cells was detected using transcriptome analysis and verified by qPCR. Flow cytometry was used to detect the effect of panobinostat on the expression of MHC Ⅰ/Ⅱ in B16F0 cells. B16F0 cells and bone marrow-derived dendritic cells (BMDC) were co-cultured to assess the effects of panobinostat on the expression of CD11c, CD80 and CD86 in BMDC cells. A xenograft mouse model was used to evaluate the effects of panobinostat on tumor growth and host immune function. Results: panobinostat promoted the acetylation of H3 and α-tubulin proteins in B16F0 cells (P < 0.01 or P < 0.001 or P < 0.000 1), inhibited cell proliferation, migration, and invasion, promoted apoptosis, and induced G1-phase cell cycle arrest (P < 0.05 or P < 0.001 or P < 0.000 1). Additionally, panobinostat enhanced surface expression of MHC Ⅰ/Ⅱ on B16F0 cells and promoted BMDC maturation (all P < 0.01). Transcriptomic analysis showed that panobinostat upregulated the expression of E-cadherin and antigen presentation related genes in B16F0 cells, and inhibited the expression of N-cadherin, vimentin, c-Myc and CDK1, which was confirmed by qPCR. In vivo, panobinostat suppressed xenograft tumor growth and enhanced immune function in tumor-bearing nude mice (P < 0.05, P < 0.000 1). Conclusion: panobinostat can inhibit the malignant biological behavior of B16F0 cells, promote apoptosis, regulate tumor immunity, and enhance immune function of tumor-bearing nude mice.
[Abstract] Objective: To investigate the effects of the histone deacetylase (HDAC) inhibitor panobinostat on melanoma growth, tumor immunity, and the underlying mechanisms. Methods: B16F0 melanoma cells were cultured and treated with different concentrations of panobinostat. The effect of panobinostat on HDAC expression in B16F0 cells was detected by WB. The effects of panobinostat on the proliferation, migration, invasion, apoptosis and cell cycle of B16F0 cells were detected by CCK-8 assay, wound-healing assay, Transwell assay and flow cytometry, respectively. The effect of panobinostat on gene expression in B16F0 cells was detected using transcriptome analysis and verified by qPCR. Flow cytometry was used to detect the effect of panobinostat on the expression of MHC Ⅰ/Ⅱ in B16F0 cells. B16F0 cells and bone marrow-derived dendritic cells (BMDC) were co-cultured to assess the effects of panobinostat on the expression of CD11c, CD80 and CD86 in BMDC cells. A xenograft mouse model was used to evaluate the effects of panobinostat on tumor growth and host immune function. Results: panobinostat promoted the acetylation of H3 and α-tubulin proteins in B16F0 cells (P < 0.01 or P < 0.001 or P < 0.000 1), inhibited cell proliferation, migration, and invasion, promoted apoptosis, and induced G1-phase cell cycle arrest (P < 0.05 or P < 0.001 or P < 0.000 1). Additionally, panobinostat enhanced surface expression of MHC Ⅰ/Ⅱ on B16F0 cells and promoted BMDC maturation (all P < 0.01). Transcriptomic analysis showed that panobinostat upregulated the expression of E-cadherin and antigen presentation related genes in B16F0 cells, and inhibited the expression of N-cadherin, vimentin, c-Myc and CDK1, which was confirmed by qPCR. In vivo, panobinostat suppressed xenograft tumor growth and enhanced immune function in tumor-bearing nude mice (P < 0.05, P < 0.000 1). Conclusion: panobinostat can inhibit the malignant biological behavior of B16F0 cells, promote apoptosis, regulate tumor immunity, and enhance immune function of tumor-bearing nude mice.
2025, 32(9):968-974.
DOI: 10.3872/j.issn.1007-385X.2025.09.010
Abstract:
[摘 要] 恶性肿瘤严重威胁人类健康，其发病机制复杂多样。脂肪量和肥胖相关蛋白（FTO）作为首个被发现的N6-甲基腺苷 （m6A）去甲基化酶，在多种肿瘤的发生发展中发挥关键作用。由于肿瘤异质性，FTO在肿瘤中呈现促癌与抑癌的双重功效，既能 抑制细胞增殖和糖酵解，诱导铁死亡、免疫调节及抑制肿瘤干细胞抗癌；又能通过促进细胞增殖、转移、增强自噬活性、调节能量 代谢及增加耐药性来促癌。深入研究FTO的分子调控机制以及FTO调节剂在肿瘤治疗中的作用，可以为肿瘤的研究与诊治提供 新的思路。
[摘 要] 恶性肿瘤严重威胁人类健康，其发病机制复杂多样。脂肪量和肥胖相关蛋白（FTO）作为首个被发现的N6-甲基腺苷 （m6A）去甲基化酶，在多种肿瘤的发生发展中发挥关键作用。由于肿瘤异质性，FTO在肿瘤中呈现促癌与抑癌的双重功效，既能 抑制细胞增殖和糖酵解，诱导铁死亡、免疫调节及抑制肿瘤干细胞抗癌；又能通过促进细胞增殖、转移、增强自噬活性、调节能量 代谢及增加耐药性来促癌。深入研究FTO的分子调控机制以及FTO调节剂在肿瘤治疗中的作用，可以为肿瘤的研究与诊治提供 新的思路。
2025, 32(9):975-982.
DOI: 10.3872/j.issn.1007-385X.2025.09.011
Abstract:
[摘 要] 嵌合抗原受体基因修饰T淋巴细胞（CAR-T细胞）疗法作为肿瘤免疫治疗的重要突破，在血液系统恶性肿瘤中展现出 显著疗效，但治疗后复发问题严重限制了其临床应用。本文系统总结了CAR-T细胞治疗后复发的关键机制，包括肿瘤抗原逃逸、 CAR-T细胞功能耗竭、免疫抑制性肿瘤微环境、肿瘤异质性及克隆演化、肿瘤干细胞耐药性等，并基于此提出新型治疗策略，如多 靶点CAR设计、联合表观遗传调控与代谢干预、重塑肿瘤微环境及人工智能辅助优化等。通过多学科交叉融合与技术创新，未 来有望突破CAR-T细胞疗法在实体瘤及复发难治性肿瘤中的瓶颈，推动精准免疫治疗的发展。
[摘 要] 嵌合抗原受体基因修饰T淋巴细胞（CAR-T细胞）疗法作为肿瘤免疫治疗的重要突破，在血液系统恶性肿瘤中展现出 显著疗效，但治疗后复发问题严重限制了其临床应用。本文系统总结了CAR-T细胞治疗后复发的关键机制，包括肿瘤抗原逃逸、 CAR-T细胞功能耗竭、免疫抑制性肿瘤微环境、肿瘤异质性及克隆演化、肿瘤干细胞耐药性等，并基于此提出新型治疗策略，如多 靶点CAR设计、联合表观遗传调控与代谢干预、重塑肿瘤微环境及人工智能辅助优化等。通过多学科交叉融合与技术创新，未 来有望突破CAR-T细胞疗法在实体瘤及复发难治性肿瘤中的瓶颈，推动精准免疫治疗的发展。
2025, 32(9):983-989.
DOI: 10.3872/j.issn.1007-385X.2025.09.012
Abstract:
[摘 要] 肿瘤微环境（TME）对肿瘤的生长发展至关重要，靶向TME是肿瘤治疗的新策略。纳米酶的酶样活性能够调节细胞的氧化还原水平，并 且在动态TME中具有协同催化活性，其在肿瘤学领域的应用已取得出色的进展。然而，纳米酶的底物选择性差、活性受TME限制、催化机制受多因 素调控等阻碍了纳米酶的推广应用。本文系统地总结了纳米酶的类型及氧化还原纳米酶的抗肿瘤作用和TME的特征，重点探讨了靶向TME纳米 酶的治疗策略及现状；同时，对基于纳米酶的增强型肿瘤治疗方法进行综述，以期推动靶向TME的肿瘤治疗纳米酶的研发及临床应用转化。
[摘 要] 肿瘤微环境（TME）对肿瘤的生长发展至关重要，靶向TME是肿瘤治疗的新策略。纳米酶的酶样活性能够调节细胞的氧化还原水平，并 且在动态TME中具有协同催化活性，其在肿瘤学领域的应用已取得出色的进展。然而，纳米酶的底物选择性差、活性受TME限制、催化机制受多因 素调控等阻碍了纳米酶的推广应用。本文系统地总结了纳米酶的类型及氧化还原纳米酶的抗肿瘤作用和TME的特征，重点探讨了靶向TME纳米 酶的治疗策略及现状；同时，对基于纳米酶的增强型肿瘤治疗方法进行综述，以期推动靶向TME的肿瘤治疗纳米酶的研发及临床应用转化。
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- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
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- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.