17β-雌二醇联合5-氮胞苷对前列腺癌细胞22RV1增殖、侵袭迁移能力的影响及其机制  

Effect of 17β-estradiol combined with 5-AzaC on proliferation,invasion and migration of human androgen-independent prostate carcinoma cell line 22RV1 in vitro and its mechanism

作　　者：胡卫锋[1] 郭永连[1] 陈琳[1] 李国灏[1] 余家俊 彭松 吴钉[1] 朱建宁[1] 

机构地区：[1]华中科技大学同济医学院附属武汉市中心医院泌尿外科,430014

出　　处：《现代泌尿生殖肿瘤杂志》2017年第6期361-365,共5页Journal of Contemporary Urologic and Reproductive Oncology

基　　金：武汉市卫计委科研课题(WX13C07)

摘　　要：目的探讨17β-雌二醇(17β-E2)联合DNA去甲基化试剂5-氮胞苷(5-AzaC)对雄激素非依赖性前列腺癌细胞22RV1增殖、侵袭迁移能力的影响及其机制。方法应用17β-E2和/或5-AzaC处理前列腺癌22RV1细胞,MTT法检测其对细胞增殖抑制的影响,并计算增殖抑制率;划痕愈合实验和Transwell实验检测其对细胞体外迁移、侵袭能力的影响;Western blot法检测雌激素受体2(ESR2)和侵袭转移相关蛋白表达的变化。结果 17β-E2和5-AzaC对前列腺癌22RV1细胞的增殖均具有不同程度的抑制作用,且呈时间依赖关系,联合用药效果明显增强(P<0.05);经17β-E2或5-AzaC处理后前列腺癌22RV1细胞体外迁移及侵袭能力均降低,且联合应用时效果更明显(P<0.05),并伴随ESR2表达的上调,基质金属蛋白酶-2(matrix metalloproteinases-2,MMP-2)、MMP-9)、p-AKT表达的下调。结论联合应用17β-E2和5-AzaC能明显抑制前列腺癌22RV1细胞的增殖、侵袭迁移能力,其作用机制可能与抑制PI3K/AKT信号通路相关,联合应用17β-E2和5-AzaC调节ESR2、MMP-2、MMP-9的表达可能是抑制雄激素非依赖性前列腺癌转移的有效方法。Objective To study the effect of 17β-E2 combined with 5-AzaC on proliferation,invasion and migration of human androgen-independent prostate carcinoma cell line 22 RV1 and its mechanism. Methods After 22 RV1 were treated with 17β-E2 and/or the DNA demethylation reagent 5-AzaC,MTT was used to detect the effect of proliferation of 22 RV1,and the proliferation inhibition rate was calculated based on the above data.Wound healing assay and transwell assay were used to study the effect of migration and invasion of 22 RV1 respectively.Western blot was used to investigate the change of ESR2,MMP-2,MMP-9 as well as p-AKT. Results It showed 17β-E2 or5-AzaC alone could at varying degree inhibit proliferation of 22 RVl cells,in a time dependent way.The effect of combination of two drugs administration was significantly increased（P〈0.05）.Migration and invasion ability of 22 RVl were significantly reduced after 17β-E2 combined with 5-AzaC treatment（P〈0.05）,accompanied by downregulation of MMP-2,MMP-9 and p-AKT expression,meanwhile upregulation of ESR2. Conclusions The use of 17β-E2 combined with 5-AzaC can effectively inhibit 22 RV1 proliferation,invasion and migration.Its mechanism may be associated with inhibition of PI3 K/AKT signaling pathway predominate.Combined use of 17β-E2 and 5-AzaC regulating the expression of ESR2,MMP-2 and MMP-9 can be an effective method to suppress metastasis of androgen-independent prostate cancer.

关 键 词：雄激素非依赖性前列腺癌 17Β-雌二醇 5-氮胞苷 增殖 侵袭迁移 

分 类 号：R737.25[医药卫生—肿瘤]