恩杂鲁胺对前列腺癌LNCaP细胞衰老的影响及其机制研究  

The Molecular Mechanisms of Cellular Senescence Induced by Enzalutamide in LNCaP Cells

作　　者：冯诗尧 李良 姚锴 闫海新 张志辉 谢栋栋[1] 

机构地区：[1]安徽医科大学第二附属医院泌尿外科,安徽 合肥

出　　处：《临床医学进展》2023年第5期7783-7789,共7页Advances in Clinical Medicine

摘　　要：探讨雄激素受体抑制剂恩杂鲁胺对人前列腺癌LNCaP细胞衰老的影响。使用CCK8实验检测LNCaP细胞对恩杂鲁胺的IC50,将加入等体积DMSO的LNCaP细胞定义为对照组,LNCaP细胞以IC50浓度的恩杂鲁胺慢性处理1个月设为实验组。β-半乳糖苷酶染色试剂盒检测细胞衰老;克隆形成实验检测细胞增殖;蛋白免疫印记实验检测雄激素受体,衰老标志蛋白的表达情况和信号转导机制。结果显示LNCaP细胞在1 μM (IC50)剂量恩杂鲁胺慢性暴露后,雄激素受体被抑制,细胞发生衰老,表现为β-半乳糖苷酶染色增多,衰老标记蛋白p16,p21表达上调。通过对信号转导研究发现,实验组中YAP1磷酸化水平降低,入核增多,YAP1可能是恩杂鲁胺致LNCaP细胞衰老的关键信号。To investigate the effect of enzalutamide, an androgen receptor inhibitor, on the senescence of hu-man prostate cancer LNCaP cells. CCK8 assay was used to detect the IC50 of LNCaP cells to enzalu-tamide. LNCaP cells supplemented with DMSO were defined as the control group, and LNCaP cells were treated with enzalutamide at IC50 concentration for one month as the experimental group. The SA-β-gal staining kit detected cell senescence. Cell proliferation was detected by colony for-mation assay. Western blot was used to detect the expression of androgen receptor and aging marker proteins and the signal transduction mechanism. The results showed that after chronic ex-posure to enzalutamide at the dose of 1 μM (IC50), the androgen receptor was inhibited. Cell senes-cence occurred in LNCaP cells, as shown by increased SA-β-gal staining and up-regulation of senes-cence marker proteins p16 and p21. Through the study of signal transduction, it was found that the phosphorylation level of YAP1 was decreased and its nuclear translocation was increased in the ex-perimental group. YAP1 may be the key signal of enzalutamide-induced senescence in LNCaP cells.

关 键 词：恩杂鲁胺 前列腺癌 LNCAP 细胞衰老 YAP1 

分 类 号：R73[医药卫生—肿瘤]