Zhu Guangbin, Wang Xinghuan, Yang Zhonghua, Cao Hong, Meng Zhe, Wang Yongzhi, Chen Dong
Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China.
Oncol Lett. 2011 Nov;2(6):1213-1217. doi: 10.3892/ol.2011.410. Epub 2011 Sep 2.
Prostate cancer is a significant health concern. In the early stages, prostate cancer cells depend on androgens for growth and survival, hence androgen-ablation therapy at this time may be effective in causing tumor regression. However, treatment options for advanced hormone-refractory prostate cancers are still relatively inefficient. This study aimed to investigate the possible effects of TRPM8 on the proliferation and angiogenesis of androgen-independent cancer PC-3 cells in vivo. Thirty male nude mice were divided into three groups: the PC-3, PC-3-vector and PC-3-TRPM8 groups. PC-3, PC-3-vector and PC-3-TRPM8 cells were respectively inoculated in the right flank to establish a transplanted tumor model. The mice were treated daily for four weeks and each group was examined by histology and immunohistochemical staining for CD34, FAK and PCNA. A CD34 marked microvascular density (MVD) test was performed. Western blot analysis was used to detect the VEGF protein expression level. Compared to the PC-3 and PC-3-vector groups, the PC-3-TRPM8 group revealed a decrease in tumor volume (P=0.000 and P=0.000, respectively), MVD (P=0.045 and P=0.041, respectively), VEGF (P=0.000 and P=0.000, respectively), FAK and PCNA. The correlation between MVD and VEGF was positive (r=0.419; P=0.021). These data show that the overexpression of TRPM8 had a negative effect on the proliferation and angiogenesis progression of PC-3 cells in vivo.
前列腺癌是一个重大的健康问题。在早期阶段，前列腺癌细胞的生长和存活依赖雄激素，因此此时的雄激素剥夺疗法可能有效地导致肿瘤消退。然而，晚期激素难治性前列腺癌的治疗选择仍然相对低效。本研究旨在探讨瞬时受体电位阳离子通道亚家族M成员8（TRPM8）对雄激素非依赖性癌PC-3细胞在体内增殖和血管生成的可能影响。将30只雄性裸鼠分为三组：PC-3组、PC-3载体组和PC-3-TRPM8组。将PC-3、PC-3载体和PC-3-TRPM8细胞分别接种于右侧腹侧以建立移植瘤模型。对小鼠进行为期四周的每日治疗，每组通过组织学和免疫组织化学染色检测CD34、粘着斑激酶（FAK）和增殖细胞核抗原（PCNA）。进行CD34标记的微血管密度（MVD）检测。采用蛋白质免疫印迹分析检测血管内皮生长因子（VEGF）蛋白表达水平。与PC-3组和PC-3载体组相比，PC-3-TRPM8组的肿瘤体积（分别为P = 0.000和P = 0.000）、MVD（分别为P = 0.045和P = 0.041）、VEGF（分别为P = 0.000和P = 0.000）、FAK和PCNA均降低。MVD与VEGF之间呈正相关（r = 0.419；P = 0.021）。这些数据表明，TRPM8的过表达对PC-3细胞在体内的增殖和血管生成进程具有负面影响。
