17AAG对胃癌细胞增殖和侵袭的影响及其作用机制研究  

Influence of 17AAG on proliferation and invasion of gastric cancer cell and its mechanism

作　　者：崔越宏[1] 余一祎[1] 刘天舒[1] 谢倩 吴伟忠[3] 刘康达[4] 

机构地区：[1] 复旦大学附属中山医院肿瘤内科, 上海200032 [2] Van Andel Research Institute [3] 复旦大学附属中山医院 肝癌研究所, 上海200032 [4] 复旦大学附属中山医院 实验研究中心, 上海200032

出　　处：《中华胃肠外科杂志》2014年第10期1031-1035,共5页Chinese Journal of Gastrointestinal Surgery

摘　　要：目的：探讨苯醌类安沙霉素药物17AAG对胃癌细胞增殖和侵袭能力的影响及其作用机制。方法17AAG作用于胃癌细胞SGC7901后，应用MTT法检测细胞增殖能力的变化；应用流式细胞术检测细胞周期的改变；应用流式细胞术和PI/Annexin Ⅴ双染色法检测细胞凋亡情况；应用Transwell实验检测细胞侵袭能力的变化；应用Western blot法检测热休克蛋白（HSP90和HSP70）及其客户蛋白（c-met和AKT）表达的改变。结果17AAG作用后，胃癌细胞SGC7901生长明显受抑，且该抑制作用呈剂量和时间依赖性；细胞周期被阻滞于G0/G1期；与空白对照组和DMSO对照组比较，17AAG处理组细胞凋亡率显著升高（P＜0．01）；侵袭能力显著下降（P＜0．01）。17AAG可上调HSP70的表达，下调HSP90客户蛋白c-met和AKT的表达，但HSP90表达无明显变化。结论17AAG对胃癌细胞SGC7901具有抑制增殖、诱导凋亡和降低侵袭能力的作用，该作用并不是通过其靶点HSP90，而是通过下调HSP90客户蛋白的表达而实现的。Objective To investigate the effect of 17-allylamino-demethoxygeldanamycin （17AAG） on the proliferative and invasive ability of gastric cancer cells and associated mechanism. Methods The proliferative ability was tested by MTT method and the cell cycle was detected by flow cytometry （FCM） when 17AAG was used to treat gastric cancer cell SGC7901. Apoptosis was detected by FCM and PI-Annexin V double staining. The invasive ability was tested by transwell method. Expression of HSP90, HSP70, c-met and AKT was detected by Western blot. Results The growth of SGC7901 cells was inhibited after the administration of 17AAG, and the inhibitation was dose- and time-dependent. The cell cycle was blocked at the G0/G1 phase. The apoptotic ratio in 17AAG group was much higher than that in blank group and DMSO group （P〈0.01）. The cellular invasive ability decreased significantly （P〈0.01）. The expression of HSP70 was elevated by 17AAG, and the expression of c-met and AKT was down-regulated, but no change of HSP90 was observed. Conclusion 17AAG can inhibit the proliferative and invasive ability of SGC7901 cells , and induces apoptosis through down-regulating the expression of HSP90 client proteins instead of the target HSP90 itself.

关 键 词：胃肿瘤 17AAG 热休克蛋白 增殖 侵袭 

分 类 号：R735.2[医药卫生—肿瘤]