雌激素受体拮抗剂氟维司群对MMQ细胞系的抗肿瘤作用及机制  

Anti-tumor effect and mechanism of estrogen receptor antagonist fulvestrant on prolactinoma MMQ cell line

作　　者：何乐[1] 李储忠[1] 王继超[2] 郭靖 张亚卓[1] 曹磊[3] He Yue;Li Chuzhong;Wang Jichao;Guo Jing;Zhang Yazhuo;Cao Lei(Cell Room,Beijing Nettrosurgical Institute,Beijing 100050,China;Department of Neurosurgery,People＇s Hospital of Xinjiang Uygur Autonomous Region,Urumqi,Xinjiang 830001,China;Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]北京市神经外科研究所细胞室,100050 [2]新疆维吾尔自治区人民医院神经外科,乌鲁木齐830001 [3]首都医科大学附属北京天坛医院神经外科,100050

出　　处：《中国微侵袭神经外科杂志》2018年第7期328-331,共4页Chinese Journal of Minimally Invasive Neurosurgery

基　　金：北京市自然科学基金资助项目(编号:7184194);首都医科大学附属北京天坛医院苗圃工程资助项目(编号:2017MP02)

摘　　要：目的探讨雌激素受体拮抗剂氟维司群对大鼠泌乳素瘤MMQ细胞系的作用及机制。方法体外培养MMQ细胞系并分为实验组和对照组。实验组分别加入浓度为0.04、1、25、625 nmol/L氟维司群,对照组加入等量DMSO。MTS法检测各组MMQ细胞增殖,流式细胞术检测细胞凋亡,ELISA检测泌乳素水平,RT-PCR和Western blot分别检测雌激素受体α(estrogen receptorα,ERα)、β-catenin和WIF-1的mRNA及蛋白表达水平。采用Wnt-β-catenin通路抑制剂SB 216763和Decitabine,观察其对细胞增殖以及β-catenin和WIF-1表达的影响。结果氟维司群可抑制细胞增殖和泌乳素的分泌,促进细胞凋亡,均呈剂量依赖性(P<0.05),IC50=32.4 nmol/L;并诱导细胞ERα和β-catenin的mRNA及蛋白的低表达,WIF-1的mRNA及蛋白的高表达(P<0.05)。与氟维司群组比较,SB 216763+氟维司群组细胞增殖明显,β-catenin的mRNA及蛋白表达升高(P<0.05)。Decitabine处理后细胞WIF-1的mRNA及蛋白表达升高,细胞增殖受到明显抑制(P<0.001)。结论氟维司群能够抑制MMQ细胞系的增殖和泌乳素的分泌,促进细胞凋亡,可能与抑制ERα的表达和抑制Wnt-β-catenin通路的激活有关。Objective To explore the effect and mechanism of estrogen receptor antagonist fulvestrant on rat prolactinoma MMQ cell line. Methods The MMQ cell line was cultured in vitro and divided into experimental group with 0.04, 1, 25, 625 nmol/L fulvestrant and control group with the same volume of DMSO. The proliferation was detected by MTS, apoptosis by flow cytometry, prolactin level by ELISA, and the mRNA and protein expressions of estrogen receptor α（ERα）, β-catenin and WIF-1 were detected by RT-PCR and Western blot. The influence of SB 216763 and Decitabine（inhibitors of Wnt-β-catenin pathway） on proliferation and expressions of β-catenin and WIF-1 were observed. Results Fulvestrant significantly inhibited cell proliferation and prolactin secretion with IC50=32.4 nmol/L, and promoted apoptosis of MMQ cells in dose-dependent way（P〈0.05）. The expressions of ERα and β-catenin mRNA and protein were inhibited and WIF-1 mRNA and protein were increased（P〈0.05）. Compared with fulvestrant group, the proliferation was increased significantly and β-catenin mRNA and protein was increased in SB 216763＋ fulvestrant group（P〈0.05）.The proliferation of MMQ cells was inhibited and expressions of WIF-1 mRNA and protein were increased after the treatment of Decitabine（P〈0.001）. Conclusions Fulvestrant could suppress the proliferation and prolactin secretion of prolactinoma MMQ cell line, and promote the apoptosis. The anti-tumor mechanism is related to the inhibition of ERα and the activation of Wnt-β-catenin pathway.

关 键 词：催乳素瘤 氟维司群 雌激素受体 通路 Wnt-β-catenin 

分 类 号：R739.41[医药卫生—肿瘤] R-33[医药卫生—临床医学]