罗格列酮诱导白血病NB4细胞凋亡的作用及机制探讨  

Peroxisome proliferator activated receptor γ agonist rosiglitazone(RGZ) induces apoptosis in leukemia NB4 cells

作　　者：刘加军[1] 刘文达[2] 刘晓丹[1] 肖若芝[1] 王春芝[1] 林东军[1] 刘培庆[3] 黄河清[3] 

机构地区：[1]中山大学附属第三医院血液科,广州市510630 [2]中山大学附属第三医院输血科,广州市510630 [3]中山大学药学院药理学与毒理学实验室,广州市510080

出　　处：《实用医学杂志》2010年第15期2679-2681,共3页The Journal of Practical Medicine

基　　金：国家自然科学基金资助项目(编号:30570786);教育部新世纪优秀人才支持计划资助项目(编号:NCET-0721);广东省自然科学基金资助项目(编号:8151008901000128)

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NB4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NB4细胞0、24、48及72h,应用RT-PCR法检测PPARγ的表达水平,MTT法检测细胞生长抑制率,流式细胞术检测细胞凋亡率。应用Western blot检测60μmol/L的RGZ作用不同时间后凋亡抑制蛋白XIAP的表达水平,同时检测不同浓度药物作用不同时间后Caspase-3活性的变化。结果:40μmol/L以上的RGZ可显著抑制细胞的生长及诱导细胞发生凋亡,呈现出明显的量-效与时-效关系。RGZ在诱导细胞凋亡的同时,PPARγ mRNA的表达水平逐渐升高,而凋亡抑制蛋白XIAP的表达水平显著下降。Western blot结果还显示Caspase-3被活化出现20kD亚单位片段。结论:RGZ可以通过PPARγ信号途径抑制NB4细胞的生长并诱导细胞发生凋亡,下调凋亡抑制蛋白XIAP的表达水平以及激活Casapse-3可能是RGZ诱导NB4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 rosiglitazone （RGZ） on leukemic NB4 cells and its mechanisms. Methods NB4 cells in culture medium in vitro were given different concentrations of PPARγ agonist RGZ （20 - 80 μmol/L）for O, 24, 48 and 72 h. The inhibitory rate of the cells were measured by MTT assay, cell apoptosis was detected by flow cytometry, and the expression of XIAP （X-linked inhibitor of apoptosis protein） protein as well as the activity of caspase-3 were also detected. Results RGZ （over 40μmol/L） could inhibit the growth of NB4 cells and cause apoptosis remarkably, the suppression was both in time- and dose-dependent manner. Western blot analysis revealed that the expression of XIAP protein was downregulated significantly and caspase-3 was activated with the appearance of its 20 kD subunit after the cells were treated by different concentrations of RGZ. Conclusion RGZ can induce apoptosis on NB4 cells effectively via PPARγ signaling pathway, downregulation the expression of XIAP protein and activation of caspase-3 may be one of its most important mechamisms.

关 键 词：白血病 过氧化物酶体增殖物激活受体 NB4细胞 细胞凋亡 

分 类 号：R733.7[医药卫生—肿瘤]