细胞周期蛋白依赖激酶5抑制剂通过调控转录与雄激素受体辅助因子在前列腺癌治疗中潜在机制的研究  

Cyclin dependent kinase 5 inhibitors regulate transcription and andrgen receptor cofactors in the treatment of prostate cancer potential mechanisms

作　　者：滕志武 张中伟 张健平 罗丽华 方俊 TENG Zhiwu;ZHANG Zhongwei;ZHANG Jianping;LUO Lihua;FANG Jun(Department of Urology,Third People Hospital of Jiujiang,Jiangxi Province,Jiujiang 332000,China)

机构地区：[1]江西省九江市第三人民医院泌尿外科,江西九江332000

出　　处：《中国当代医药》2025年第9期7-10,17,共5页China Modern Medicine

基　　金：江西省卫生健康委科技计划项目(202311556)。

摘　　要：目的观察细胞周期蛋白依赖激酶5(CDK5)抑制剂通过调控转录与雄激素受体(AR)辅助因子在前列腺癌治疗中的潜在作用机制。方法选取80株人前列腺癌细胞株DU145作为研究对象,根据细胞处理方法的不同分为CDK5抑制剂组(n=40)与对照组(n=40),CDK5抑制剂组予以CDK5siRNA干扰DU145细胞内CDK5表达,对照组未予以特殊处理。分析CDK5抑制剂对去势抵抗前列腺癌细胞株DU145的生长抑制率,比较两组锌指E-box结合同源盒1(Zeb1)波形蛋白、AR蛋白的表达量。结果CDK5抑制剂组患者24h的去势抵抗前列腺癌细胞株DU145的生长抑制率指标低于本组48、72h,差异有统计学意义(P<0.05);CDK5抑制剂组24、48.、72h对肿瘤细胞的生长抑制率高于对照组,差异有统计学意义(P<0.05)。CDK5抑制剂组Zeb1、波形蛋白、AR蛋白低于对照组,差异有统计学意义(P<0.05)。结论CDK5、AR降低活性及表达水平可经由波形蛋白/Zeb1信号通路对去势抵抗性前列腺癌细胞DU145的转移侵袭、恶性增殖进行抑制。Objective To investigate the potential mechanism of cyclin dependent kinase 5(CDK5)inhibitors in prostate cancer therapy by regulating transcription and androgen receptor(AR)cofactors.Methods Eighty human prostate cancer cell lines DU145 were selected as the study object,and they were divided into CDK5 inhibitor group(n=40)and control group(n=40)according to different cell treatment methods.CDK5 siRNA interfered with the expression of CDK5 in DU145 cells in the CDK5 inhibitor group,while no special treatment was given to the control group.The growth inhibition rate of CDK5 inhibitors on castration-resistant prostate cancer cell line DU145 was analyzed,and the expression levels of zinc finger E-box binding homeobox 1(Zebl),Vimentin and AR protein were compared between the two groups.Results The growth inhibition rate of castration-resistant prostate cancer cell line DU145 in CDK5 inhibitor group at 24 h was lower than that at 48 and 72 h,the dfferences were statistically significant(P<0.05).The growth inhibition rate of CDK5 inhibitor group was higher than that of control group at 24,48 and 72 h,and the differences were statistically significant(P<0.05).The proteins of Zeb1,Vimentin and AR in CDK5 inhibitor group were lower than those in control group,and the differences were statistically significant(P<0.05).Conclusion The decreased activity and expression levels of CDK5 and AR can in-hibit the metastasis,invasion and malignant proliferation of castration-resistant prostate cancer cells DU145 through Vimentin/Zebl signaling pathway.

关 键 词：细胞凋亡 转移侵袭 前列腺癌 雄激素受体 细胞周期蛋白依赖激酶5 

分 类 号：R737.25[医药卫生—肿瘤]