Targeting TR4 nuclear receptor alters prostate cancer cell MDV3100-sensitivity

【作者】 陈学栋； 张会江； 李朋； 李恭会；

【机构】 丽水市人民医院； 浙江大学附属邵逸夫医院；

【摘要】 目的:While anti-androgen Enzalutamide (MDV3100) showed promising therapeutic benefit with extended 4.8months survival to castration resistant prostate cancer (PCa) patients,it invariably developed resistance that involved the induction of androgen receptor (AR) splicing variant ARv7.方法:We established C4-2 scr/siTR4,22Rv1 scr/siTR4,C4-2 Vector/TR4,22Rv1 Vector/TR4,and MDV3100-resistant C4-2 cell line.MTS test was applied to test MDV3100-sensitivity(IC50) of PCa cells with differential TR4expression.结果:TR4 and AR-V7 were overexpressed in MDV3100-resistant C4-2 cell line compared to parental Enzalutamidesensitive cells.Addition of functional TR4 in C4-2 cells led to increase MDV3100-resistance.In contrast,knockingdown TR4 with TR4-siRNA in C4-2 cells resulted in increasing MDV3100-sensitivity.Altered TR4 expression led to change ARv7 expression revealed that AR-V7 was positively correlated to the TR4 expression.结论:TR4 may influence the MDV3100 sensitivity of PCa via altering the expression of AR-V7.Targeting TR4 in PCa cells could influence their MDV3100-sensitivity.更多还原