罗格列酮对白血病K562细胞的诱导凋亡作用及其作用机制  

Apoptosis inducing effect of peroxisome proliferator-activated receptor V agonist on K562 cells and its mechanism

作　　者：胡婷[1] 徐妍[1] 王春芝[1] 刘加军[1] 肖若芝[1] 林东军[1] 潘祥林[2] 

机构地区：[1]中山大学附属第三医院血液科,广州510630 [2]山东大学第二医院血液

出　　处：《国际肿瘤学杂志》2008年第11期874-877,共4页Journal of International Oncology

基　　金：国家自然科学基金资助项目（30570786）;教育部新世纪优秀人才支持计划资助项目（NCET-06-0721）

摘　　要：目的探讨过氧化物酶体增殖物激活受体γ（PPARγ）激动剂罗格列酮（rosiglitazone，RGZ）对白血病K562细胞的诱导凋亡作用及其作用机制。方法以不同浓度的RGZ（20～80μmoL／L）作用于体外培养的K562细胞0、24、48、72h，应用噻唑蓝法检测细胞生长抑制率，用膜联蛋白V-碘化丙啶双染法检测细胞凋亡，并对细胞凋亡前后P53蛋白的表达水平及Caspse-3活性进行检测。结果40μmol／L以上的RGZ可显著抑制细胞生长及诱导细胞发生凋亡，呈现出明显的量效与时效关系，在细胞凋亡的同时，P53蛋白的表达水平及Caspse-3活性均明显升高。结论40μmol／L以上的RGZ能显著抑制K562细胞的生长并诱导细胞发生凋亡，升高半胱天冬蛋白酶（Caspse）-3活性，上调促凋亡蛋白P53的表达水平是RGZ诱导K562细胞发生凋亡的重要作用机制之一。Objective To investigate the apoptosis inducing effect of peroxisome proliferator-activated receptor γ （PPARγ） agonist on leukemic K562 cells and its mechanisms of action. Methods K562 cells in culture medium in vitro were given different concentrations of PPARs, agonist rosiglitazone （RGZ） （20-80 μmol/L） for 0,24,48 and 72 h. The inhibitory rate of the cells were measured by MTT assay, cell apoptosis was detected by Annexin V/PI staining, and the expression of P53 protein as well as the activity of caspase-3 were also detected. Results RGZ （ over 40 μmol/L） could inhibit the growth of K562 cells and cause apoptosis remarkably, the suppression was both in time-and dose-dependent manner. The expression of P53 protein was upregulated and the activity of caspase-3 was increased concomitantly after the cells were treated by RGZ. Conclusion PPARy agonist RGZ（ over 40 μmol/L） can induce apoptosis on K562 cells significantly, upregu- lation the expression of P53 protein as well as increasing caspase-3 activity may be one of its most important mechamisms.

关 键 词：过氧化物酶体增殖物激活受体 细胞凋亡 白血病 

分 类 号：R285[医药卫生—中药学]