DLC-1通过Rho通路抑制耐恩杂鲁胺前列腺癌细胞的增殖与侵袭能力  

Deleted in liver cancer-1 inhibits the proliferation and invasion of enzalutamide-resistant prostate cancer cells via the Rho pathway

作　　者：汤洋斌 杨果 吴小候[1] 全真 Tang Yangbin;Yang Guo;Wu Xiaohou;Quan Zhen(Department of Urology,The First Affiliated Hospital of Chongqing Medical University)

机构地区：[1]重庆医科大学附属第一医院泌尿外科,重庆421800

出　　处：《重庆医科大学学报》2024年第10期1061-1066,共6页Journal of Chongqing Medical University

基　　金：国家自然科学基金资助项目(编号:81802543)。

摘　　要：目的:探索肝癌缺失因子1(deleted in liver cancer 1,DLC-1)对耐恩杂鲁胺前列腺癌(prostate cancer,PCa)细胞增殖,侵袭和凋亡的影响以及作用机制。方法:体外以不同浓度的恩杂鲁胺药物培养人前列腺癌lncap及C4-2细胞株6个月以上,构建恩杂鲁胺耐药细胞系lncap-R,C4-2-R。CCK-8法检测其IC50,验证恩杂鲁胺耐药株是否构建成功。利用慢病毒转染lncap-R,C4-2-R,以敲低和过表达DLC-1,采用克隆实验、Transwell实验和流式细胞术检测DLC-1对耐恩杂鲁胺的前列腺癌细胞的增殖、侵袭和凋亡的影响。结果:与对照组相比,过表达组DLC-1显著抑制了2个耐药株的增殖和侵袭进程。机制上,WB实验结果表明DLC-1表达与2个耐药株中Rho蛋白的表达呈负相关。Rho抑制剂rhosin逆转了因敲低DLC-1后lncap-R细胞凋亡减少的情况。结论:DLC-1可以下调耐药株中的Rho蛋白的表达,并抑制耐药株的增殖和侵袭。Objective:To investigate the effect of deleted in liver cancer-1(DLC-1)on the proliferation,invasion,and apoptosis of enzalutamide-resistant prostate cancer cells and its mechanism of action.Methods:Hμmol/Lan prostate cancer lncap and C4-2 cell lines were cultured in vitro with different concentrations of enzalutamide for more than 6 months,and enzalutamide-resistant cell lines were constructed as lncap-R and C4-2-R.IC50 was measured by CCK-8 assay to verify the successful construction of enzalutamide-resistant cell lines.lncap-R and C4-2-R were transfected by lentivirus to achieve the knockdown and overexpression of DLC-1,and colony formation assay,Transwell assay,and flow cytometry were used to observe the effect of DLC-1 on the proliferation,invasion,and apoptosis of enzalutamide-resistant prostate cancer cells.Results:Compared with the control group,the overexpression group showed that DLC-1 significantly inhibited the proliferation and invasion of the two enzalutamide-resistant cell lines.As for mechanism of ac-tion,Western blot showed that the expression of DLC-1 was negatively correlated with the expression of Rho protein in both enzalutamide-resistant cell lines.The Rho inhibitor rhosin reversed the reduction in the apoptosis of lncap-R cells due to knockdown of DLC-1.Conclusion:DLC-1 can downregulate the expression of Rho protein in drug-resistant cell lines and inhibit their prolifera-tion and invasion.

关 键 词：肝癌缺失因子1 前列腺癌 恩杂鲁胺 RHO蛋白 增殖 侵袭 

分 类 号：R737.25[医药卫生—肿瘤]