热休克蛋白90抑制剂对PC-3M细胞杀伤效应的研究  

Influence of HSP90-inhibitor on the proliferation of prostate carcinoma cells PC-3M

作　　者：骆雨[1] 庞自力[1] 

机构地区：[1]华中科技大学协和医院泌尿外科,武汉430022

出　　处：《临床泌尿外科杂志》2005年第9期581-583,共3页Journal of Clinical Urology

基　　金：湖北省自然科学基金资助课题(项目编号:2004ABA223)

摘　　要：目的:观察热休克蛋白90(HSP90)抑制剂对前列腺癌PC-3M细胞增殖活性、细胞周期和凋亡的影响,初步探讨其作用机制。方法:采用四甲基偶氮唑盐(MTT)比色法检测不同浓度的HSP90抑制剂对PC-3M细胞增殖的影响;采用细胞免疫化学测定HSP90抑制剂对PC-3M细胞HER-2表达的影响;采用流式细胞分析术(FCM)检测细胞凋亡和细胞周期。结果:高浓度(500 nmol/L)HSP90抑制剂可杀伤PC-3M细胞,低浓度(10、50、125、250 nmol/L)条件下则主要发挥生长抑制作用。HSP90抑制剂可使PC-3M细胞HER-2表达水平降低,并在500 nmol/L浓度时诱导细胞凋亡。结论:HSP90抑制剂较为明显地抑制PC-3M细胞生长,并在高浓度时杀伤癌细胞;其作用机制可能与下调HER-2的表达有关。Objective：To examine the effects of HSP90 inhibitor on the growth, cell cycle and apoptosis of PC- 3M cell line, and to explore the possible mechanisms. Methods：The effects of diverse concentrations HSP90-inhibitor on the proliferation of PC-3M cell line were assayed by rypan blue exclusion and tetrazolium （MTT）. The expression of HER-2 in PC-3M was assayed by immunohistochemical SP method. The effects of HSP90-inhibitor on the cell cycle distribution and apoptosis induction of PC-3M were evaluated with flowcytometry （FCM）. Results： A higher dosage of HSP90-inhibhor （500 nmol/L） had a cytotoxic effect on PC-3M cells, while lower dosage from 10nmol/L to 250nMol/L produced a predominant inhibiting effect. FCM analysis manifested that HSP90-inhibitor high dosage of 500 nmol-Lcould induced apoptosis, and at the other concentrations, G1 arrest. Conclusions： HSP90-inhibitor could suppress the proliferation of PC-3M cell line and induced apoptosis at high dosage. This effect might result from reducing the expression of HER-2 in PC-3M cell line.

关 键 词：热休克蛋白90 前列腺癌 细胞凋亡 

分 类 号：R737.25[医药卫生—肿瘤]