c-Jun和CBP在槲皮素抑制前列腺癌中的作用  

The roles of c-Jun and CBP in the inhibitory effect of quercetin on prostate cancer cells

作　　者：苑辉卿[1] 郭怀芳[2] 贺美兰[1] 孔峰[1] 胡晓燕[1] 姜安丽[1] 徐霞[1] 张建业[1] Charles YF Young 

机构地区：[1]山东大学医学院生物化学与分子生物学教研室 [2]山东大学药学院天然药物化学教研室 [3]Department of Urology,Mayo Clinic College of Medicine,Mayo Clinic,Rochester,MN 55905,USA

出　　处：《药学学报》2006年第9期819-824,共6页Acta Pharmaceutica Sinica

基　　金：山东省自然科学基金资助项目(Y2004C24)

摘　　要：目的探讨槲皮素抑制前列腺癌的作用机制。方法应用蛋白印迹技术检查槲皮素(quercetin)对雄激素受体(androgen receptor,AR)的辅调节因子c-Jun和cAMP应答元件结合蛋白的结合蛋白[cAMP response elem entb ind ing prote in(CREB)-b ind ing prote in,CBP]蛋白表达的影响;利用细胞转染技术检测c-Jun和CBP对AR功能的影响;免疫沉淀技术检验c-Jun与AR的蛋白-蛋白相互作用。结果槲皮素能够明显诱导c-Jun的高表达,高表达的c-Jun能够抑制AR的功能。槲皮素对CBP的蛋白表达水平无明显影响,而增加CBP的表达并不能逆转槲皮素对AR功能的抑制作用。免疫沉淀结果表明,c-Jun与AR存在蛋白-蛋白相互作用。结论槲皮素抑制前列腺癌的机制可能是通过c-Jun与AR的蛋白相互作用,而不是通过c-Jun竞争结合AR的辅激活因子CBP来实现的。Aim To further uncover the possible mechanism of quercetin-mediated inhibitory effect on prostate cancer cells. Methods The cell extracts treated with quercetin or without treatment were used for checking protein expression levels of c-Jun and cAMP response element binding protein （CREB）- binding protein （CBP） by Western blotting assay. Regulatory effects of c-Jun and CBP on the function of androgen receptor （AR） were examined by cotransfection experiment. Finally, a physical interaction of c-Jun and the AR was investigated by coimmunoprecipitation. Results Quercetin dramatically induced the protein expression of c-Jun which in turn inhibited the AR function. Meanwhile, quercetin had no detectable effect on CBP expression, and the results of transient transfection demonstrated that the ectopic CBP stimulated the transcriptional activity of AR, whereas CBP-mediated stimulation could be attenuated by quercetin. Furthermore, physical interaction of c-Jun and the AR was confirmed by coimmunoprecipitation result. Conclusion Overexpression of c-Jun induced by quercetin had inhibitory effect on the function of AR protein, and increased CBP expression did not reverse the inhibition by quercetin. Together, quercetin-mediated inhibition on the AR function might be not by competition with limited amount of CBP in the cell, but through a direct association of c-Jun and the AR.

关 键 词：c—Jun CBP 槲皮素 雄激素受体 前列腺癌 细胞株 

分 类 号：R963[医药卫生—微生物与生化药学]