摘要
目的研究2-脱氧葡萄糖联合雷帕霉素对人结肠癌的抗肿瘤作用。方法运用MTT细胞增殖试验、克隆形成试验以及Transwell侵袭试验考察药物对HCT-116细胞株的增殖、克隆及侵袭的影响,通过蛋白印迹技术分析信号通路蛋白cleavedCaspase-3、Bax/Bcl-2、LC3-II、Akt、S6K的变化情况,进行初步的机制研究。结果 MTT试验显示,2-脱氧葡萄糖可增强雷帕霉素对HCT-116细胞增殖、克隆和侵袭的抑制作用。蛋白印迹分析表明,高剂量2-脱氧葡萄糖可引起Bax/Bcl-2比值增加,活化Caspase-3,引起细胞凋亡;低剂量2-脱氧葡萄糖可拮抗雷帕霉素对肿瘤细胞生长和增殖的抑制作用。结论 2-脱氧葡萄糖通过抑制肿瘤细胞的糖酵解,增强雷帕霉素对结肠癌HCT-116细胞凋亡的诱导作用。
Objective To evaluate the anti-tumor effect of rapamycin combined with 2-deoxy-D-glucose(2-DG) on the human colon cancer. Methods HCT-116 cell lines were treated with rapamycin, 2-DG and rapamycin plus 2-DG respectively. The MTT cell viability assay, colony-forming unit assays and transwell assay were performed to investigate the effect of rapamycin combined with 2-DG on cell proliferation, colony formation and invasion. The expression levels of Bax/Bcl-2, LC3-II, S6 K, and cleaved Caspase-3 and the changes in Akt(protein kinase B) activity were examined by Western blotting. Results Rapamycin suppressed the cell proliferation, clone formation and invasion of HCT-116 cell lines. Rapamycin combined with high dose 2-DG enhanced the ratio of Bax/Bcl-2 and Caspase-3 activity; while low dose 2-DG reduced rapamycin activity. Conclusion 2-DG enhances rapamycin-induce apoptosis of colon cancer HCT-116 cell lines, which may be correlated with excessive mitochondria stress response.
出处
《世界临床药物》
CAS
2015年第6期400-404,共5页
World Clinical Drug
