白藜芦醇与奥沙利铂联合应用抑制结直肠癌细胞增殖的机制  

Mechanism of inhibitory effect of oxaliplatin in combination with resveratrol on colorectal cancer

作　　者：常环环 杨姝[1] 李文帅[1] 孙海梅[1] 吴波[1] 周德山[1] 

机构地区：[1]首都医科大学基础医学院组织学与胚胎学教研室肿瘤侵袭和转移机制研究北京市重点实验室,北京100069

出　　处：《解剖学杂志》2017年第2期125-128,136,共5页Chinese Journal of Anatomy

基　　金：国家自然科学基金(81300285;81572322;31371220)

摘　　要：目的:探讨联合应用白藜芦醇与奥沙利铂抑制结直肠癌细胞系增殖的作用机制。方法:单独或联合应用奥沙利铂和白藜芦醇处理人结肠癌细胞系HCT-116和HT-29,CCK-8实验检测肿瘤细胞活力,流式细胞术检测细胞周期;应用慢病毒介导使HCT-116细胞过表达miR-34c,再用奥沙利铂处理,检测肿瘤细胞的活力和凋亡;建立结直肠癌皮下荷瘤裸鼠模型,分别给予二甲基亚砜、奥沙利铂、白藜芦醇及白藜芦醇+奥沙利铂,制作肿瘤组织石蜡切片进行Ki67染色并计数。结果:与单独应用奥沙利铂或白藜芦醇相比,联合应用奥沙利铂和白藜芦醇更显著抑制HCT-116细胞的活力,细胞阻滞在G1期。荷瘤裸鼠实验同样显示奥沙利铂和白藜芦醇联合应用较单独应用时Ki67阳性率减少。结论:联合应用奥沙利铂和白藜芦醇具有协同抑制结直肠癌细胞增殖的作用,其可能机制与白藜芦醇促进结直肠癌细胞抑癌基因miR--34c表达有关。Objective： To investigate the mechanism of inhibitory effect of oxaliplatin（Oxa） in combination with resveratrol （Res） on eolorectal cancer （CRC）. Methods： CRC cell line HCT-116 and HT-29 cells were treated with Res, Oxa or Res＋ Oxa. CCK-8 kit was used to detect tumor cell activity and flow cytometry was used to detect cell cycle. MiR-34c was over- expressed in HCT-116 cells by lentiviral infection followed by the treatment of Oxa; then, tumor cell activity was detected. Xenografts of HCT-116 cells were generated in BALB/c nude mice, which were administered with DMSO, Oxa, Res or Res＋ Oxa. The tumor was measured. Two weeks later, the tumor tissues were detected with Ki67. Results： Compared with Res or Oxa treatment, Res＋Oxa treatment inhibited cell viability more significantly and induced more cell cycle arrest at G1 phase in vitro. Similarly, combination of Res and Oxa significantly inhibited tumor growth in vivo indicated by the decrease of the positive rate of Ki67 compared with Res or Oxa treatment. Furthermore, upon the treatment of Oxa, the cell viability of HCT-116 cells over-expressing miR-34c was significantly inhibited compared with that of the controls. Conclusion： Combination of Res and Oxa has marked synergistic effect on the inhibition of CRC cell proliferation, which may be due to the increased expression of tumor suppressor gene miR-34c by Res.

关 键 词：白藜芦醇 奥沙利铂 结直肠癌 miR-34c 

分 类 号：R735.34[医药卫生—肿瘤]