TRPM8对前列腺癌PC-3细胞增殖和迁移能力影响的研究

摘要

We investigated the effects of transient receptor potential M8 (TRPM8) channel on the proliferation and motility of androgen-independent prostate cancer PC-3 cells. After being permanently transfected with an empty vector and eDNA encoding the TRPM8 protein, cells were analysed for cell cycle distribution and motility using flow cytometry and scratch assay, lmmunocytoehemistry and Ca2+ imaging analysis revealed the overexpression of functional TRPM8 channel on both endoplasmic reticulum and plasma membrane of PC-3-TRPM8 cells. Cell cycle distribution and scratch assay analysis revealed that TRPM8 induced cell cycle arrest at the G0/G1 stage (P < 0.05) and facilitated the cell apoptosis induced by starvation (P < 0.05). Furthermore, TRPM8 inhibited the migration of PC-3-TRPM8 cells (P<0.01) through the inactivation of focal-adhesion kinase. It appears that TRPM8 was not essential for the survival of PC-3 cells; however, the overexpression of TRPM8 had negative effects on the proliferation and migration of PC-3 cells. Thus, TRPM8 and its agonists may serve as important targets for the treatment of prostate cancer.%本文探讨瞬时受体电位通道M8(TRPM8)对于雄激素非依赖性前列腺癌细胞PC-3增殖和迁移能力的影响.将PC-3细胞分别稳定转染空载体和编码TRPM8蛋白的质粒后,分别通过流式细胞术和划痕试验检测细胞周期分布和体外迁移能力.细胞免疫荧光化学和ca2+浓度检测提示,在Pc-3-TRPM8细胞中高表达的TRPM8蛋白不仅位于内质网,而且位于胞浆膜.细胞周期分析结果提示TRPM8诱导细胞周期阻滞于Go/G1期(P<0.05),同时TRPM8能易化由饥饿诱导的细胞凋亡(P<0.05).此外,TRPM8能通过灭活FAK降低PC-3-TRPM8细胞的迁移能力(P<0.01).因此,TRPM8并不是PC-3细胞存活所必需的离子通道;相反,高表达的TRPM8蛋白能抑制PC-3细胞的增殖和迁移.TRPM8或许能作为前列腺癌治疗的一个新标靶.