HSP90在乳腺癌细胞增殖中的作用与机制研究

目的： 应用热休克蛋白90(HSP90)功能特异性抑制剂格尔德霉素(GA)研究HSP90在乳腺癌细胞增殖中的作用，进而探讨相关机制。方法: 培养人乳腺癌细胞株MDA-MB-435s，采用MTT法检测GA对MDA-MB-435s细胞的生长抑制作用，流式细胞术分析细胞周期，应用Western免疫印迹法检测细胞内Stat3磷酸化状态和突变型p53表达变化。结果: 不同浓度GA对乳腺癌MDA-MB-435s细胞有生长抑制作用，呈时效量效依赖关系，GA作用后细胞呈现G2/M期阻滞。400 nmol/L GA作用48h后，细胞内Stat3磷酸化水平明显低于对照组，同时突变型p53表达明显低于对照组。结论: 抑制HSP90功能可明显抑制乳腺癌MDA-MB-435s细胞的增殖，此与下调细胞内Stat3磷酸化水平和突变型p53表达有关。

Effect of heat shock protein 90 on proliferation of human breast cancer cells and its molecular mechanisms

AIM: To investigate the effect of heat shock protein 90(HSP90) on proliferation of human breast cancer cells by a specific inhibitor for HSP90,geldanamycin(GA),and to analyze its molecular mechanisms.METHODS: Human breast cancer cell line MDA-MB-435s was used as a model.Proliferation of MDA-MB-435s cell was measured with MTT assay.Cell cycle was analyzed by flow cytometry.Alteration of phosphorylated Stat3 protein and mutant p53 protein in cells was detected by Western blotting.RESULTS: Geldanamycin inhibited the proliferation of MDA-MB-435s cells in time-and dose-depending manners.After treatment with GA,MDA-MB-435s cell cycle was arrested at G2/M phase.The levels of phosphorylated protein Stat3 and mutant p53 protein in MDA-MB-435s cells were reduced obviously by 55% and 48% respectively after 48 hour treatment with GA at the concentration of 400 nmol/L,compared to control cells.CONCLUSION: Inhibition of HSP90 function can prevent breast cancer cell proliferation significantly,which may be related to down-regulatin of the phosphorylated Stat3 protein and mutant p53 protein in the cells.