抑制热休克蛋白gp96对HepG2细胞中hTERT表达及细胞增殖的影响  

The impact on hTERT expression and cell proliferation in HepG2 cells by inhibition of heat shock protein gp96

作　　者：吴信华[1] 庄红芹[2] 姚登福[3] 戚菁[1] 施维[1] 鞠少卿[1] 

机构地区：[1]南通大学附属医院外科综合实验室,江苏226001 [2]南京大学医药生物技术国家重点实验室 [3]南通大学临床医学研究中心

出　　处：《交通医学》2012年第2期116-118,123,共4页Medical Journal of Communications

基　　金：南通市社会发展科技计划项目(S2008053)

摘　　要：目的:探讨热休克蛋白90抑制剂戈尔德霉素(geldanamycin,GA)对HepG2细胞中gp96、人端粒酶逆转录酶(hTERT)表达的影响及对HepG2细胞增殖的抑制作用。方法:以Western blot方法检测不同浓度GA作用下,HepG2细胞中HSP90α、gp96及hTERT的表达。用MTT法检测GA作用下HepG2细胞的增殖抑制情况。同时构建HSP90αsiRNA质粒,转染HepG2细胞后观察对hTERT的影响。结果:HepG2细胞中HSP90α、gp96及hTERT的表达均明显高于正常肝细胞LO-2,导入HSP90αsiRNA质粒的HepG2细胞HSP90α表达减少,但gp96、hTERT的表达与对照组HepG2比较差异无统计学意义。加入GA后HepG2细胞中HSP90α、gp96及hTERT表达均显著减少,HepG2细胞增殖也明显受抑。结论:GA可通过gp96抑制HepG2细胞中hTERT表达及HepG2细胞增殖,gp96有望成为肝癌分子治疗新的靶点。Objective： To investigate the impact on expression of gp96 and hTERT and the inhibition of cell proliferation in HepG2 cells by the HSP90 inhibitor GA. Methods： The expression of gp96 and hTERT in HepG2 ceils was detected by western blot with a series of different concentrations of GA. The inhibition of HepG2 cell proliferation was ana- lyzed by MTF. HSP90a siRNA plasmid was constructed and transfected into HepG2 cells. Results： There was a significant difference in the expression of HSP90a, gp96 and hTERT between HepG2 cells and normal hepatocyte LO-2. The expression of HSP90a decreased in HepG2 cells which was transfected with HSP90asiRNA plasmid, while no statistical difference in gp96 and hTERT was found compared with the control group. The expression of HSP90a, gp96 and hTERT reduced as well as the proliferation was inhibited significantly in HepG2 cells when 10μmol/L had been added. Conclusion： The expression of hTERT and the cell proliferation could be inhibited by GA with gp96 in HepG2 cells, gp96 may be a new target for hepatoma molecular therapy.

关 键 词：原发性肝细胞癌 HepG2 热休克蛋白90 GP96 戈尔德霉素 Westernblot检测法 人端粒酶逆转录酶 

分 类 号：R735.7[医药卫生—肿瘤]