大豆异黄酮激活PPARγ,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

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。

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 ~/ （PPAR~/）. Methods PPAR~/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 PPAR~/, for 48 h. The expression and distribution of PPAR~/ were detected by immunofluorescence staining. Cell apoptosis was determined by TUNEL assay and Annexin V/P! 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 PPAR~/expression in DU-145 ceils were not significant after treatment with either genistein or daidzein, but PPAR~/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 PPAR~/nucleus translocation were significantly inhibited. Conclu- sion Soy isoflavones promote apoptosis in human prostate cancer DU-145 cells through PPAR7 activation.