Rapamycin抑制PI3K/AKT/mTOR信号通路对胃癌MGC-803细胞影响  

Inhibitory effect of rapamycin on PI3K/AKT/m TOR signaling pathway in gastric adenocarcinoma MGC-803 cells

作　　者：陈晓伟[1] 徐余超 孙海翔[1] 赵颖[1] 刘梦琪[1] 张文文[1] 沈孝兵[1] 

机构地区：[1]东南大学公共卫生学院环境医学工程教育部重点实验室,江苏南京210009

出　　处：《中国公共卫生》2017年第4期602-606,共5页Chinese Journal of Public Health

基　　金：国家自然科学基金(81172619;81472940)

摘　　要：目的探讨rapamycin作用于胃癌细胞株MGC-803后对细胞生长影响及其作用机制。方法体外培养胃癌细胞株MGC-803,使用不同浓度rapamycin干预MGC-803细胞。采用MTT法检测细胞增殖变化;实时荧光定量PCR(QPCR)检测关键基因的表达;蛋白印迹法(WB)检测相关蛋白的表达;流式细胞术检测细胞周期及凋亡的变化。结果与对照组相比,rapamycin对胃癌MGC-803细胞的增殖活性有明显的抑制作用,呈现出剂量依赖性(P<0.05)。Rapamycin显著抑制PI3K、AKT、m TOR、4EBP、P70S6K基因的m RNA表达,差异有统计学意义(P<0.05);Rapamycin能抑制p-m TOR、p-P70S6K蛋白的表达;Rapamycin将细胞周期阻滞在G0/G1期,并诱导细胞凋亡(P<0.05)。结论靶向m TOR抑制剂rapamycin可通过调控PI3K/AKT/m TOR信号通路进而调控胃癌细胞的生长。Objective To investigate the effect of rapamycin on growth of gastric carcinoma cell line MGC-803 and to explore its possible mechanism. Methods Human gastric cancer cell line MGC-803 cells were cultured in vitro and treated with rapamycin of different concentrations. The proliferation of MGC-803 cells was detected with 3-（4,5-dimeth- ylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay;the expressions of mRNA of relevant genes were deter-mined with quantitative real-time PCR （QPCR） and the expressions of related proteins were detected with Western blot; the changes in cell cycle and apoptosis were measured with flow cytometry. Results Compared to that of the control group, the proliferation of MGC-803 cells treated with rapamycin was downregulated in a dose-dependent manner （ P 〈 0. 05 ）. Rapamycin significantly downregulated the expressions of mRNA of phosphatidylinositol 3-kinase （PI3K）, pro-tein kinase B （AKT）, mammalian target of rapamycin （mTOR） ,4EBP, and P70S6K （P 〈 0. 05 for all）. Rapamycin downregulated expressions of p-roTOR and p-P70S6K. The cell cycle of MGC-803 cells treated with rapamycin was arrested mainly in the G0/G1 stage, and apoptosis of the MGC-803 cells was observed （ P 〈 0.05 ）. Conclusion Rapamycin can inhibit the grouth of MGC-803 cells by regulating the PI3K/AKT/mTOR signaling pathway.

关 键 词：胃癌 P13K/AKT/mTOR信号通路 雷帕霉素 细胞周期 增殖 凋亡 

分 类 号：R735.2[医药卫生—肿瘤]