IFN-γ和TNF-α诱导间充质干细胞促进结肠癌细胞的化疗抵抗  

IFN-γ and TNF-α treated mesenchymal stem cells can enhance the chemotherapy resistance of colon cancer cells

作　　者：李蓉[1] 盛丹丹[2] 赵雪[3] 井莹莹[1] 张黎[2] 韩志鹏[1] 

机构地区：[1]第二军医大学东方肝胆外科医院肿瘤免疫与基因治疗实验室,上海200438 [2]第二军医大学长海医院药学部,上海200433 [3]上海交通大学医学院附属仁济医院中心实验室,上海200127

出　　处：《第二军医大学学报》2016年第1期40-45,共6页Academic Journal of Second Military Medical University

摘　　要：目的观察炎症因子干扰素γ(interferon-γ,IFN-γ)和肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)诱导间充质干细胞(mesenchymal stem cells,MSCs)对结肠癌细胞化疗抵抗的影响及机制。方法应用炎症因子IFN-γ和TNF-α联合处理MSCs,收集条件培养上清,并将其作用于人结肠癌细胞系HCT116及HT29细胞,同时分别给予化疗药物顺铂和5-氟尿嘧啶处理。显微镜下观察各组细胞形态变化,MTT法和流式细胞术检测细胞增殖和凋亡情况,RT-PCR检测凋亡相关基因Bax和Bcl-2表达情况。结果经化疗药物处理,与未经条件培养上清培养的细胞比较,经条件培养上清培养的细胞形态学改变更轻微,细胞增殖率增高(P<0.05)、凋亡率降低(P<0.05),Bcl-2 mRNA表达水平上调、Bax mRNA表达水平下调。结论经炎症因子IFN-γ和TNF-α诱导的MSCs能够促进结肠癌细胞化疗抵抗能力。Objective To observe the influence of interferon-γ（IFN-g） and tumor necrosis factor-α （TNF-a）treated mesenchymal stem cells （MSCs） on the chemotherapy resistance of colon cancer cells （CRCs） and to discuss the related mechanism. Methods The supernatants of MSCs treated with IFN-7 and TNF-a were collected and used, together with chemotherapy drug cisplatin and 5-fluorouracil, to treat HCTll6 and HT29 CRCs. Then the cellular morphology was observed under microscope, and the cell proliferation and apoptosis were examined by MTT and PI/Annexin V-FITC assay. Furthermore, the mRNA levels of Bax and Bcl-2 were detected by RT-PCR. Results The CRCs treated with the supernatant of MSCs exposed to inflammatory factors, compared to CRCs treated with the supernatant of MSCs not exposed to inflammatory factors, had a slighter morphology changes, a significantly higher proliferation rate （P〈 0. 05）, and a significantly lower apoptosis rate following chemotherapy（P〈0. 05）. Moreover, Bcl-2 mRNA level was higher and Bax mRNA level was lower in CRCs treated with the supernatant of MSCs exposed to inflammatory factors. Conclusion MSCs stimulated with inflammation factors IFN-g and TNF-α can promote the chemotherapy resistance of human CRCs.

关 键 词：干扰素Γ 肿瘤坏死因子α 间质干细胞 结肠肿瘤 肿瘤抗药性 

分 类 号：R735.35[医药卫生—肿瘤]