大豆异黄酮激活PPARγ促进人前列腺癌DU-145细胞凋亡

目的探讨染料异黄酮(genistein,GEN)和大豆苷元(daidzein,DAI)对人前列腺癌DU-145细胞凋亡的影响及其与过氧化物酶体增殖物激活体受体γ(peroxisome proliferators-activated receptorγ,PPARγ)的关系。方法采用过氧化物酶体增殖物反应元件(peroxisome proliferator responsive element,PPRE)驱动的荧光素酶报告基因检测GEN、DAI对DU-145细胞PPARγ的激活作用;GEN、DAI单独或联合PPARγ选择性拮抗剂GW9662处理DU-145细胞,采用免疫荧光化学染色方法观察PPARγ定位分布变化;TUNEL法和AnnexinⅤ/PI双染色流式细胞术检测细胞凋亡的变化。结果 GEN、DAI明显增强转染PPRE-TK-Luc质粒的DU-145细胞中荧光素酶表达活性,且这种作用可被GW9662所逆转。GEN或DAI单独作用于DU-145细胞时,PPARγ发生核移位;细胞凋亡率明显增加(P<0.05)。GW9662分别与GEN或DAI联合作用时,GEN、DAI促进PPARγ核移位和诱导细胞凋亡的作用明显削弱(P<0.05)。结论大豆异黄酮可通过激活PPARγ信号途径,促进人前列腺癌DU-145细胞凋亡。

Soy isoflavones promotes apoptosis in human prostate cancer DU-145 cells through PPARγ activation

Objective To investigate the effect of genistein(GEN) and daidzein(DAI) on apoptosis in human prostate cancer DU-145 cells and their correlation with peroxisome proliferators-activated receptor γ(PPARγ).Methods PPARγ activity in prostate cancer DU-145 cells treated with soy isoflavones was mea-sured by peroxisome proliferator responsive element(PPRE)-driven luciferase reporter gene assay.DU-145 cells were respectively treated genistein and daidzein alone and either of them combined with GW9662,which was a selective inhibitor of PPARγ,for 48 h.The expression and distribution of PPARγ were detected by immunofluorescence staining.Cell apoptosis was determined by TUNEL assay and AnnexinⅤ/PI dual-color flow cytometry.Results Genistein and daidzein significantly enhanced luciferase expression activity in DU-145 cells transfected with PPRE-TK-Luc plasmid,and the effect could be reversed by GW9662.The changes of PPARγ expression in DU-145 cells were not significant after treatment with either genistein or daidzein,but PPARγ translocation to nucleus increased.The apoptotic rate of DU-145 cells treated with genistein or daidzein increased significantly(P<0.05).When cells were treated with either genistein or daidzein combined with GW9662,the increased apoptosis rate and PPARγ nucleus translocation were significantly inhibited.Conclusion Soy isoflavones promote apoptosis in human prostate cancer DU-145 cells through PPARγ activation.