中国肿瘤生物治疗杂志2018，Vol.25Issue(10)：999-1005,7.DOI:10.3872/j.issn.1007-385x.2018.10.005
PD-1抗体增强奥沙利铂体内外抗结肠癌的效果
PD-1 antibody enhanced anti-tumor efficacy of oxaliplatin against colon cancer in vitro and in vivo
摘要
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+TCMand TEMRAratio (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.关键词
奥沙利铂/PD-1抗体/结肠癌/CD8+T细胞Key words
oxaliplatin (OXA)/PD-1 antibody/colon cancer/CD8+T cell分类
医药卫生引用本文复制引用
钟根深,孙智洋,陈亚楠,许芝山,杨如,吴敏娜,石焕,路平..PD-1抗体增强奥沙利铂体内外抗结肠癌的效果[J].中国肿瘤生物治疗杂志,2018,25(10):999-1005,7.基金项目
国家自然科学青年基金资助项目(No.81602709 （）
81872361) （）
河南省高校重点科研资助项目(No.15A320063,No.16A310022) （No.15A320063,No.16A310022）
河南省骨干青年教师培养计划(No.2016GGJS-105) （No.2016GGJS-105）
