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瞬时受体电位阳离子通道亚家族M成员8(TRPM8)对体内前列腺癌PC-3细胞增殖和血管生成的影响。

Effects of TRPM8 on the proliferation and angiogenesis of prostate cancer PC-3 cells in vivo.

作者信息

Zhu Guangbin, Wang Xinghuan, Yang Zhonghua, Cao Hong, Meng Zhe, Wang Yongzhi, Chen Dong

机构信息

Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China.

出版信息

Oncol Lett. 2011 Nov;2(6):1213-1217. doi: 10.3892/ol.2011.410. Epub 2011 Sep 2.

Abstract

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.

摘要

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。

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