PPARa激动剂非诺贝特诱导前列腺癌DU145细胞氧化损伤和凋亡的作用

目的探讨过氧化物酶体增殖因子激活受体α激动剂非诺贝特诱导雄激素非依赖性前列腺癌DU145细胞氧化损伤和凋亡的作用及可能机制。方法用0、50、100μmol/L浓度的非诺贝特作用于DU145细胞,24h后利用荧光显微镜和流式细胞仪检测各组细胞中活性氧、超氧化物阴离子、一氧化氮含量和细胞凋亡率的变化。Westernblot检测细胞内凋亡相关蛋白BCL-2和BAX的表达变化。结果不同浓度非诺贝特作用细胞后细胞凋亡率显著上调,活性氧、超氧化物阴离子和一氧化氮含量较对照组明显上升并呈剂量依赖性(P<0.05)。50μmol/L非诺贝特作用后,DU145细胞内BCL-2表达明显下调,BAX表达升高。结论非诺贝特能诱导前列腺癌细胞DU145氧化损伤和细胞凋亡,其机制可能与氧化应激增强及抗凋亡蛋白表达下降有关。

Fenofibrate induces oxidative stress and apoptosis in the prostate cancer cell line DU145

Objective To study the effects of fenofibrate on oxidative damage and apoptosis of androgen-independent prostate cancer cell line DU145, and to explore its possible mechanism. Methods Effects of fenofibrate on DU145 cells were evaluated by Flow cytometer, fluorescence, RT PCR and Western blot analysis. Results There were significant differences in reactive oxygen species, superoxide anion and nitric oxide of DU145 cells in different fenofibrate concentration groups （P~0.05）. Furthermore, fenofibrate could enhance mitochondrial depolarization in a dose depend- ent manner. Compared with the control group, the ratios of apoptosis in DU145 cells was signifi- cantly higher than those of controls （P~0.05）. The protein level of BCL-2 decreased significantly after the exposed to fenofibrate at the concentration of 50 /~mol/L. Conclusions Fenofibrate can induce cell apoptosis mediated by oxidative stress, the mechanism may be related to suppress the ex- pression of BCL-2.