检索历史 清除

目的 观察人工合成酪蛋白激酶2(CK2)选择性抑制剂四溴肉桂酸(TBCA),对各种前列腺癌细胞株雄激素受体(AR)反式激活、细胞增殖和活力的效应.方法 TBCA和基因特异性小干扰RNA(siRNA)应用到前列腺癌细胞株,Alamar blue法检测细胞生长,流式细胞术检测细胞周期分布,荧光素酶基因报道分析检测AR反式激活,免疫荧光法检测AR核定位以及定量聚合酶链反应(PCR)检测AR介导的基因表达.结果 TBCA呈剂量依赖性抑制细胞增殖和细胞周期停滞在G2/M期,半抑制浓度值(IC50)为25 mol/L.TBCA阻断AR核转位和基因表达(P＜0.01).2种CK2催化亚单位都参与雄激素刺激的核转位和AR介导的基因表达(P＜0.05).结论 CK2α和CK2α’亚单位都参与了AR信号转运表达,TBCA有可能成为一种有效的前列腺癌化学治疗药物.

Objective To investigate the role of casein kinase 2 (CK2) selective inhibitor tribromoisocyanuric acid (TBCA) in androgen receptor (AR) transactivation,cell proliferation and viability in prostate cancer cell lines,and explore a new chemotherapy for prostate cancer.Methods Prostate cancer cell lines were prepared.With TBCA treatment,Alamar-blue assay was performed to assess cell proliferation and viability in C4-2 cells and flow cytometry was performed for cell cycle analysis in C4-2 and 22Rvl cells; while immunofluorescence staining was performed to determine AR nuclear translocationin in PC-3/AR cells with R1881 pretreatment,and luciferase gene reporter assay was performed to determine AR transactivation in LNCaP cells; Reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the mRNA level of prostate specific antigen (PSA).Results With TBCA treatment,Alamar-blue reading decreased in a dose-dependent manner,and the 50％ inhibitory concentration ( IC50 ) was around 25 mol/L.Significant G2/M arrest was detected in C4-2 and 22Rvl cells.R1881-induced AR nuclear localization was reduced significantly ( P ＜ 0.01 ).R1881 -stimulated ARE-LUC reporter activity in LNCaP cells decreased with reduced level of PSA mRNA,which was an AR endogenous target( P ＜ 0.05 ).Conclusion The selective CK2 inhibitor TBCA can dramatically inhibite cell proliferation and cause a G2/M phase arrest in prostate cancer cells.