中文摘要：

目的：探讨TRPM8抑制剂BCTC对前列腺癌DU145细胞的抑癌作用。方法：PCR和Western blot检测TRPM8的表达;MTT法检测DU145细胞增殖能力;划痕实验、transwell实验检测细胞迁移和侵袭能力;流式细胞术检测细胞周期和凋亡;Western blot检测周期相关蛋白（p-AKT,p-GSK-3β,cyclin B1,cyclin D1,CDK2/4/6）、凋亡相关蛋白（Bcl-2,Bax,caspase-3）、迁移相关蛋白（pFAK,MMP2）表达水平的变化。结果：PCR和Western blot提示TRPM8在前列腺癌DU145细胞中表达显著高于正常前列腺上皮PNT1A细胞;BCTC处理后,DU145细胞增殖能力下降（P〈0.05）,细胞周期表现为G0/G1阻滞期（P〈0.05）,迁移、侵袭能力也明显下降（P〈0.05）,但凋亡相关实验显示BCTC并不引起细胞凋亡（P〉0.05）。Western blot显示BCTC能下调p-AKT,cyclin D1,CDK2,CDK6,MMP2和pFAK等的表达,而上调p-GSK-3β的表达。结论：TRPM8抑制剂BCTC能抑制前列腺癌DU145细胞增殖、迁移和侵袭能力,是一个极具潜力的抗前列腺癌药物。

英文摘要：

Objective：To investigate the anti-tumor activity of BCTC,apotent and representative inhibitor of TRPM8 in prostate cancer DU145 cells.Methods：TRPM8expression was detected by PCR and western blot.The effect of BCTC on DU145 cells was analysed by MTT,flow cytometry analysis,scratch motility and transwell invasion assays.Molecular mechanism was investigated by series of Western blot assays.Results：TRPM8expression was found much higher in tumoral prostate DU145 cells than normal prostate PNT1 Acells,at both mRNA and protein levels.The data provide evidence that blockade of TRPM8 by BCTC reduced viability of DU145 cells but not PNT1 Acells.Besides,BCTC also inhibited cell cycle progression,migration and invasion of DU145.Cell cycle-related proteins such as p-AKT,cyclin D1,CDK2 and CDK6 werefound down-regulated by BCTC,while p-GSK-3βup-regulated.And motility-related proteins MMP2 and pFAK were found down-regulated.Nevertheless,BCTC failed to trigger obvious apoptosis of DU145,which was clarified by series of apoptosis-related experiments.Conclusion：TRPM8specific antagonist BCTC showed excellent anti-tumor activity in prostate cancer DU145 cells,which reveals that TRPM8-targeted blockade by its specific antagonist BCTC is a high potential targeted therapeutic strategy against prostate cancer.