白介素-6经SRC-1诱导卵巢癌细胞对他莫昔芬耐药的机制研究  

Mechanism of Interleukin-6 Resistance to Tamoxifen by SRC-1 Induced Ovarian Cancer Cells

作　　者：宋姜楠 孙旸 刘金龙 杨静[1] 陈晓[2] 王越 SONG Jiang-nan;SUN Yang;LIU Jin-long;YANG Jing;CHEN Xiao;WANG Yue(Department of Pathogenic Biology,Logistics College of Chinese People's Armed Police Forces,Tianjin 300309,China;Department of Gynaecology and Obstetrics,Special Medical Center of Chinese People's Armed Police Forces,Tianjin 300162,China;Institute of Disaster Medicine,Tianjin University,Tianjin 300072,China;Health Team of PLA 31696 Army,Jinzhou,Liaoning 121000,China)

机构地区：[1]中国人民武装警察部队后勤学院病原生物学教研室,天津300309 [2]中国人民武装警察部队特色医学中心妇产科,天津300162 [3]天津大学灾难医学研究院,天津300072 [4]中国人民解放军31696部队卫生队,辽宁锦州121000

出　　处：《解放军医药杂志》2019年第12期39-44,共6页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：国家自然科学基金项目(81572852);天津市自然科学基金项目(18JCZDJC33200)

摘　　要：目的研究白介素-6(IL-6)诱导下卵巢癌细胞对他莫昔芬(TAM)产生耐药的分子机制。方法应用不同质量浓度的IL-6处理A2780细胞,应用编码正义IL-6 cDNA和反义IL-6 cDNA的质粒分别转染A2780细胞和CAOV-3细胞,RT-PCR和Western Blot法检测外源性和内源性IL-6对卵巢癌细胞类固醇受体共激活因子-1(SRC-1)和SRC-3的mRNA和蛋白表达的影响。应用编码SRC-1的质粒和SRC-1 shRNA分别转染A2780细胞和CAOV-3细胞,Western Blot法检测SRC-1的蛋白表达,MTT法检测SRC-1的蛋白表达对细胞TAM敏感性的影响。结果外源性和内源性过表达IL-6均可明显促进A2780细胞SRC-1的mRNA和蛋白表达,而对SRC-3表达无影响;抑制IL-6表达可下调CAOV-3细胞SRC-1的mRNA和蛋白水平,而对SRC-3表达无影响。过表达SRC-1的A2780细胞对TAM的耐药性增加,抑制SRC-1表达的CAOV-3细胞对TAM的敏感性增加。结论IL-6可能通过促进SRC-1的表达进而活化雌激素受体信号通路,诱导卵巢癌细胞对TAM耐药。Objective To investigate molecular mechanism of ovarian cancer cells induced by interleukin-6(IL-6)to Tamoxifen(TAM)resistance.Methods A2780 cells were treated with different concentrations of IL-6.Plasmids encoding plus sense IL-6 and antisense IL-6 cDNA were transfected into A2780 and CAOV-3 cells respectively.Effects of exogenous and endogenous IL-6 on expressions of steroid receptor coactivator-1(SRC-1)and SRC-3 in ovarian cancer cells were detected by reverse transcription-polymerase chain reaction(RT-PCR)and Western Blot methods.Plasmids encoding SRC-1 and SRC-1 shRNA were respectively transfected into A2780 and CAOV-3 cells.Expression of SRC-1 protein was detected by Western Blot method,and effect of SRC-1 protein expression on TAM sensitivity was detected by MTT method.Results Both exogenous and endogenous overexpression of IL-6 could significantly promote expressions of SRC-1 mRNA and protein in A2780 cells,but they had no effect on SRC-3 expression.Inhibition of IL-6 expression could down-regulate expressions of SRC-1 mRNA and protein in CAOV-3 cells,while SRC-3 expression had no effect.Drug resistance of overexpressed SRC-1 in A2780 cells to TAM was increased,and sensitivity of inhibited SRC-1 expression in CAOV-3 cells to TAM was also increased.Conclusion IL-6 may activate estrogen receptor signaling pathway and induce resistance to TAM in ovarian cancer cells by promoting SRC-1 expression.

关 键 词：白介素-6 卵巢肿瘤 他莫昔芬 类固醇受体共激活因子 抗药性 肿瘤 雌激素受体Α 

分 类 号：R737.[医药卫生—肿瘤]