过氧化物酶体增殖激活物受体γ配体诱导肾癌细胞的凋亡  

Peroxisome proliferator-activated receptor γ ligands induce apoptosis of renal cell carcinoma

作　　者：杨风光[1] 黄世清[1] 龚书榕[1] 施作霖[1] 辛殿旗[2] 张志文[2] 管又非[2] 郭应禄[2] 吴阶平[2] 

机构地区：[1]福建省立医院泌尿外科,福州350001 [2]北京大学泌尿外科研究所

出　　处：《中华实验外科杂志》2010年第3期309-311,共3页Chinese Journal of Experimental Surgery

基　　金：福建省科技人才创新项目（2005J072）

摘　　要：目的观察过氧化物酶体增殖激活物受体γ（PPARγ）配体对肾癌细胞凋亡的影响。方法通过ELISA方法观察0～100μmol／L浓度的吡格列酮和曲格列酮（TZDs）对肾癌细胞786-0、A498及正常肾细胞HK-2、HMCC凋亡的影响，Heochst33342荧光染色、DNA片段化分析检测70．00μmol／L吡格列酮或80．00μmol／L曲格列酮处理后肾癌细胞的凋亡，Westernblot观察TZDs处理后肾癌细胞凋亡调控蛋白bcl-2／bax的表达变化及Caspase-3活性的改变。结果超过50．00μmol／L的TZDs可诱导肾癌细胞出现凋亡，LC50值分别为65．11μmol／L（曲格列酮／786—0）、67．73μmol／L（吡格列酮／786—0）、63．91μmol／L（曲格列酮／A498）和78．12μmol／L（吡格列酮／A498），但对正常。肾细胞没有影响。荧光染色显示80．00μmol／L的吡格列酮及70．00μmol／L的曲格列酮处理后。肾癌细胞明显凋亡，伴随bcl-2蛋白的表达水平降低和bax蛋白的增加，Caspase-3的活性明显增强，在48h可达到基础值的3．5～4．5倍。结论激活PPARγ可以诱导肾癌细胞的凋亡，PPARγ有可能成为肾细胞癌新的治疗靶点。Objective To investigate the induction of apoptosis by peroxisome proliferator-activated receptor γ（PPARγ） in renal cell carcinoma （RCC）-derived cell lines. Methods ELISA was performed to determine the cell death induced by 0-100 μmol/L PPARγ ligands （pioglitazone and troglitazone,TZDs） in two RCC-derived cell lines （7862-O and A498） and two normal kidney （NK）-derived cell lines （HK2 and HMCC）. Cells were treated with 70. 00 μmol/L pioglitazone or 80. 00 μmol/L troglitazone to evaluate apoptosis by fluorescence microscopy and DNA ladder assay. The mutativc expression of bcl-2 and bax before and after TZDs treatment was detected by Western blotting, and the activation of Caspase-3 was also explored. Results Treatment of more than 50. 00 μmol/L TZDs for 48 h could induce cell death in RCC-derived cells,with the LC50 of 65.11 μmol/L （troglitazone/786-O） ,67.73 μmol/L （ pioglitazone/ 786-0） ,63.91 μmol/L （ troglitazone/A498 ） and 78.12 μmol/L （ pioglitazone/A498 ）, respectively. Typical apoptosis was induced by 80. 00 μmol/L pioglitazone or 70. 00 μmol/L troglitazone in 786-0 and A498 cells. Under TZDs treatment,a decrease in bcl-2 expression and increase in BAX expression in a time-dependent manner were seen in both 786-0 and A498 cells. Moreover,the activation of Caspase-3 was up-regulated. Conclusion The results reveal that PPAR-γ ligands have the tumor-suppressive effect on RCC cells. PPAR-γ may be the candidates target for a novel approach to the treatment of RCC.

关 键 词：肾肿瘤 PPARΓ 脱噬作用 

分 类 号：R737.11[医药卫生—肿瘤]