曲格列酮诱导肾癌细胞的凋亡  

Peroxisome proliferator-actived receptor-γ ligand troglitazone induces apoptosis in renal cell carcinoma

作　　者：杨风光[1] 张志文[2] 辛殿祺[1] 师长进[1] 武学清[1] 刘武江[1] 郭应禄[1] 吴阶平[1] 

机构地区：[1]北京大学第一医院泌尿外科泌尿外科研究所 [2]北京大学基础医学院生理学系,北京100083

出　　处：《北京大学学报（医学版）》2004年第2期173-176,共4页Journal of Peking University:Health Sciences

摘　　要：目的 :探讨过氧化物酶增殖体激活的受体γ(PPAR γ)在肾癌细胞中的表达及PPAR γ配体曲格列酮对肾癌细胞凋亡的影响。方法 :通过RT -PCR、Westernblot方法 ,从mRNA及蛋白水平检测PPAR γ在肾癌细胞株786 O、A4 98及正常肾来源的细胞株HK 2、HMCC中的表达 ,DNA梯度电泳、荧光显微镜观察曲格列酮诱导肾癌细胞凋亡的现象 ,Westernblot检测Bcl 2、Bax蛋白在肾癌细胞凋亡过程中的变化。结果 :PPAR γ在肾癌细胞株中的表达高于正常肾来源的细胞株 ,5 0 μmol/L曲格列酮可以诱导肾癌细胞凋亡 ,伴随有Bcl 2表达的减少及Bax表达的增加。结论 :曲格列酮可以诱导肾癌细胞的凋亡 ,PPARObjective: To investigate the expression of peroxisome proliferator actived receptor γ (PPAR γ)and the inducement of apoptosis by PPAR γ ligand in renal cell carcinoma(RCC) derived cell lines.Methods:RT-PCR and Western blot analysis were performed to determined the expression of PPAR γ mRNA and protein in two RCC derived cell lines(786 O and A498) and two normal kidney(NK) derived cell lines(HK 2 and HMCC). Two RCC cell lines were treated with 50 μmol/L troglitazoned for and evaluated for the effects of antidiabetic thiazolidinediones (TZDs) on the cells apoptosis by fluorescence microscopy and DNA ladder assay.The mutative expressions of Bcl 2 and Bax before and after TZDs treatment were also performed by western blot analysis. Results: The expression of PPAR γ was observed to be stronger in 786 O and A498 cells than in HK 2 and HMCC cells by RT-PCR and Western blot analysis. Treated with 50 μmol/L troglitazone (for 48 h) it induced typical apoatosis in 786 O and A498 cells. After treatment, a decrease in Bcl 2 expression in RCC cells was observed by Western blot analysis,and the expression of Bax,however,was up regulated.Conclusion: The results reveal that troglitazone has the tumor suppressive effect on RCC cells. High affinity PPAR γ ligands (TZDs) may be the candidates for a novel approach to the treatment of this refractory neoplasm.

关 键 词：曲格列酮 肾癌细胞 细胞凋亡 PPAR-Γ 肿瘤抑制 细胞培养 给药方式 

分 类 号：R965[医药卫生—药理学] R737.11[医药卫生—药学]