普萘洛尔抑制前列腺癌发展的分子机制  

Molecular Mechanisms of Propranolol Inhibits the Progression of Prostate Cancer

作　　者：王仕钦[1] 江春[2] 黄卫 黄辉虎[1] WANG Shiqin;JIANG Chun;HUANG Wei;HUANG Huihu(Department of Suegery,Hainan Provincial Hospital of Traditional Chinese Medicine,Haikou 570203,China;Department of Urology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China)

机构地区：[1]海南省中医院外二科,海口570203 [2]中山大学孙逸仙纪念医院泌尿外科,广州510120

出　　处：《医药导报》2020年第6期763-770,共8页Herald of Medicine

摘　　要：目的探讨普萘洛尔抑制前列腺癌发生、发展的分子机制。方法采用Real-Time qPCR检测miR-382和SETD8 mRNA的表达,Western blotting检测细胞内SETD8、p53、p21、凋亡相关蛋白(Bcl-2、Bax和Caspase 9)和转移相关蛋白(N-cad、E-cad和Vimentin)的表达水平,CCK-8检测细胞增殖能力,双荧光素酶报告基因系统检测miR-382对SETD8的靶向调控作用,Transwell侵袭实验检测细胞迁移能力,构建荷瘤小鼠动物模型验证普萘洛尔在动物体内对前列腺癌的抑制作用。结果 miR-382在前列腺癌组织和细胞中显著下调,而SETD8显著上调,两者呈负相关。普萘洛尔能够通过miR-382调控SETD8/p53/p21通路,抑制前列腺癌细胞增殖和迁移,并促进细胞凋亡,延长荷瘤小鼠存活时间。结论普萘洛尔能够通过miR-382/SETD8/p53/p21分子轴抑制前列腺癌的发展和转移。Objective To investigate the mechanisms of propranolol in the treatment of prostate cancer.Methods Real-Time qPCR was employed to detect the expression levels of miR-382 and SETD8 mRNA;Western blotting was used to evaluate SETD8,p53,p21,apoptosis-associated proteins(including Bcl-2,Bax and Caspase 9)and metastasis-associated proteins(including N-cad,E-cad and Vimentin)expression levels.CCK-8 assay was performed to investigate cell proliferative ability and the dual luciferase reporter system was employed to explore the mechanisms of miR-383 targeting SETD8.Transwell assay was used to detect cell migration.Animal models was established to verify the inhibiting effects of propranolol on prostate cancer in vivo.Results Compared to normal cells and tissues,miR-382 downregulated and SETD8 upregulated in prostate cancer cells and tissues.Propranolol inhibited prostate cancer cell proliferation and migration,promoted cell apoptosis and prolonged survival time of tumor bearing mice by regulating miR-382/SETD8/p53/p21 pathway.Conclusion Propranolol inhibited prostate cancer progression via modulating miR-382/SETD8/p53/p21 pathway.

关 键 词：普萘洛尔 前列腺癌 miR-382基因 SETD8酶 小分子核糖核苷酸 

分 类 号：R972[医药卫生—药品] R737[医药卫生—药学]