哺乳动物雷帕霉素靶蛋白调控前列腺癌22RV1细胞雄激素受体及Akt磷酸化  

Mammalian target of rapamycin regulates androgen receptor and Akt phosphorylation in prostate cancer 22RV1 cells

作　　者：潘腾飞[1] 梁朝朝[1] 陈先国[1] 樊松[1] 

机构地区：[1]安徽医科大学第一附属医院泌尿外科,安徽合肥230022

出　　处：《中华男科学杂志》2013年第12期1068-1071,共4页National Journal of Andrology

基　　金：教育部博士点基金(20113420110003);安徽省自然科学基金(1208085MH138)~~

摘　　要：目的:探索哺乳动物雷帕霉素靶蛋白mTORC1和mTORC2在前列腺癌22RV1细胞增殖及凋亡中的作用。方法:噻唑蓝(MTT)比色法检测mTORC1和mTORC2沉默后前列腺癌22RV1细胞增殖改变;流式细胞术(FCM)检测mTORC1和mTORC2沉默后前列腺癌22RV1细胞凋亡;Western印迹检测mTORC1和mTORC2沉默后前列腺癌22RV1细胞雄激素受体(AR)和Akt磷酸化表达。结果:MTT显示mTORC1沉默后,前列腺癌22RV1细胞的生长率无明显变化(P>0.05),而mTORC2沉默后,细胞的增殖受到了显著抑制(P<0.01);FCM显示mTORC1沉默后,细胞的凋亡率明显增加(P<0.01),而mTORC2沉默后,细胞的凋亡率无明显变化(P>0.05);Western印迹检测显示mTORC1沉默后,前列腺癌22RV1细胞中AR和Akt磷酸化表达显著增加(P<0.05),而mTORC2沉默后则显著抑制了前列腺癌22RV1细胞中AR和Akt磷酸化表达(P<0.05)。结论:mTORC2对于前列腺癌22RV1细胞的存活是必需的,mTORC2有可能成为治疗前列腺癌的一个有意义的靶点。Objective： To investigate the roles of the mammalian target of rapamycin-1 and -2 （mTORC1 and TORC2 ） in the proliferation and apoptosis of prostate cancer 22RV1 cells. Methods： After silencing mTORC1 and TORC2, we examined the proliferation and apoptosis of prostate cancer 22RV1 cells by methyhhiazol tetrazolium （MTF） assay and flow cytometry, respectively, and detected the expressions of the androgen receptor （AR） and Akt phosphorylation in the prostate cancer 22RV1 cells by Western blot after transfecting Raptor-siRNA and Rictor-siRNA to the 22RV1 cells. Results： MTT showed that the prostate cancer 22RV1 cells had no significant change in the growth rate after mTORC1 silence （P 〉 0.05 ）, but their proliferation was markedly inhibited af- ter mTORC2 silence （P 〈0.01 ）. Flow cytometry revealed a dramatic increase in the apoptosis of the 22RV1 cells after mTORC1 si- lence （ P 〈 0.01 ）, but no obvious change after mTORC2 silence （ P 〉 0.05 ）. Western blot exhibited that mTORC1 silence significant- ly increased the expression of AR and Akt phosphorylation （ P 〈 0.05 ）, while mTORC2 silence markedly decreased them （ P 〈 0.05 ）. Conclusion： mTORC2 is not only required for the survival of prostate cancer 22RV1 cells, but also a promising therapeutic target of prostate cancer.

关 键 词：SIRNA 哺乳动物雷帕霉素靶蛋白 前列腺癌 22RV1细胞 

分 类 号：R737.25[医药卫生—肿瘤]