格尔德霉素对肝癌细胞Akt磷酸化及细胞周期的影响  

Effects of geldanamycin on PKB/Akt phosphorylation and cell cycle in human hepatoma HepG2 cells

作　　者：马昕[1] 林菊生[1] 杨志芳[2] 黎培员[1] 宋东坡[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肝病研究所,湖北省武汉市430030 [2]华中科技大学同济医学院附属同济医院普外科,湖北省武汉市430030

出　　处：《世界华人消化杂志》2004年第8期1793-1795,共3页World Chinese Journal of Digestology

摘　　要：目的:研究热休克蛋白90抑制剂格尔德霉素(geldanamycin, GA)对肝癌细胞生长的影响并探讨相关机制. 方法:用MTT法检测药物对肝癌HepG2细胞的生长抑制作用,并用流式细胞术分析细胞周期与凋亡状况.Western印记杂交法检测细胞内蛋白激酶B/AKT磷酸化状态的变化. 结果:400μmoL/L浓度的GA处理细胞后,HepG2细胞胞内磷酸化AKT的水平明显下降(24.h为对照组66.03%,48 h 为对照组34.02%);GA作用后细胞呈现G2/M期阻滞并伴有凋亡率增加;同时MTT法显示GA对HepG2细胞有生长抑制作用,用药时间越长抑制率越高,24h和48h的抑制率分别为4.09%和21.74%. 结论:通过GA抑制Hsp90的功能能够抑制肝癌细胞的生长并促进其凋亡,这一效应与信号传导系统活化状态的改变有关.AIM: To study the anti-proliferation effects of inhibitor of heat shock protein 90 (Hsp90), geldanamycin (GA), and its mechanism on human hepatoma HepG2 cells. METHODS: MTT assay was used to detect the effect of growth inhibition of HepG2 cells. Cell cycle and apoptosis were analyzed by flow cytometry. Alteration of phospho-rylated Akt was analyzed by Western blot assay. RESULTS: GA significantly inhibited growth of HepG2 cells. After 24 or 48 h treatment with GA, the level of phosphorylated Akt was reduced significantly. It was about 66.0% (24 h) and 34.0% (48 h) compared to that of control cells. G2/M arrest was also prominent. The rate of apoptosis increased from 3.2% to 8.1% after 24 h treatment and from 4.0% to 11.42% after 48 h treatment, respectively. CONCLUSION: The functional Hsp90 is important for the growth of hepatoma cells. It may be a promising way to cure liver cancer using the inhibitor of Hsp90.

关 键 词：肝癌细胞 HepG2细胞 磷酸化 细胞周期 对照组 MTT法 生长抑制作用 霉素 HSP90 蛋白激酶B 

分 类 号：R735.7[医药卫生—肿瘤] R737.25[医药卫生—临床医学]