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Archive > Volume 25 Issue 10 > 2018,25(10):999-1005. DOI:10.3872/j.issn.1007-385X.2018.10.005 Prev Next
Basic Research
PD-1 antibody enhanced anti-tumor efficacy of oxaliplatin against colon cancer in vitro and in vivo
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Abstract:
Objective: To explore the anti-tumor effects of oxaliplatin (OXA) combined with PD-1 antibody on colon cancer. Methods:Flow cytometry was used to detect the expression of PD-L1 in colon cancer cell lines HCT-116 and HT-29. Co-culture method was used to detect the secretion of cytokines and the changes of CD4/CD8 subsets in T-cells that co-cultured with HCT-116 cells, which were pretreated with OXA in combination with/without PD-1 antibody; The CT26 transplanted tumor model of colon cancer in BALB/c mice was established and treated with the combination of OXA and PD-1 to evaluate their anti-tumor efficacy. Meanwhile, CD8 antibody was used to scavenge CD8+ T cells in mice, and to evaluate the role of CD8+ T cells in the anti-tumor effect of OXA in vivo. Results:OXA could significantly increase the expression of PD-L1 on the surface of colon cancer cells. Compared with pure T-cells, the T cells co-cultured with colon cancer HCT-116 cells that pre-treated by OXA, exhibited significantly reduced IL-2, IFN-γ and TNF levels (all P<0.05) in its culture supernatant and decreased ratio of CD4+ memory T cell / CD8+TEMER (P<0.05), whereas there was increased cell proportion of the CD4+ (P>0.05) and CD8+ (P<0.05) na?ve T cells. After co-treated with PD-1 antibody, compared with the single treatment of OXA, IFN-γ and IL-10 content (P<0.05) in culture supernatant and the subsets of CD8+ TCM and TEMRA ratio (P>0.05) were increased. In vivo experiments showed that OXA combined with PD-1 antibody could enhance its anti-tumor activity, the tumor suppression rates were 25.6% (OXA) and 29.1% (αPD-1), respectively, however, the rate of tumor inhibition was increased to 58.2% when combined (P<0.05, compared to OXA or αPD-1 group). After scavenging CD8+ T cells in mice, the antitumor activity of OXA dropped from 68.4% to 46.2% (P<0.05). Conclusion: OXA combined with PD-1 antibody had synergistic anti-tumor effect, and CD8+ T cells played an important role in the antitumor activity of OXA.
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Project Supported:
Project supported by the National Natural Science Foundation for Youth Scientists of China (No.81602709; 81872361), the Key Scientific Research Projects for Higher Education of Henan Province (No. 15A320063, No.16A310022), and the Young Backbone Teachers Fellowship in Henan Province (No.2016GGJS-105)
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