白细胞介素-6对人卵巢癌细胞中雌激素受体亚型的调控作用  

Regulation Effect of Interleukin-6 on Estrogen Receptor Isoforms in Human Ovarian Cancer Cells

作　　者：张桐硕[1,2] 马晓霞 宋姜楠 李艳秋[2] 杨静[1] 王越[1] ZHANG Tong-shuo;MA Xiao-xia;SONG Jiang-nan;LI Yan-qiu;YANG Jing;WANG Yue(Department of Pathogenic Organism,Logistics University of People＇s Armed Police,Tianjin 300309,China;a.Department of Clinical Laboratory,b.Department of Gynecology ＆ Obstetrics,2.Affiliated Hospital of Logistics College of People＇s Armed Police,Tianjin 300162,China;Department of Immunology,Tianjin Medical University,Tianjin 3000703,China)

机构地区：[1]武警后勤学院病原生物学教研室,天津300309 [2]武警后勤学院附属医院检验科,天津300162 [3]天津医科大学免疫学系,天津3000703 [4]武警后勤学院附属医院妇产科,天津300162

出　　处：《解放军医药杂志》2018年第11期14-19,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;81273520);天津市自然科学基金资助项目(18JCZDJC33200);武警后勤学院科学技术研究项目(WHB201505)

摘　　要：目的研究白细胞介素-6(IL-6)对雌激素受体(ER)亚型表达水平的影响,探讨二者在卵巢癌内分泌治疗耐药机制中的关系。方法从癌症基因图谱(TCGA)数据库获取535例卵巢癌样本,分别按IL-6和ER亚型相关基因表达的高低比较卵巢癌的无进展生存率,并分析总体IL-6基因与ER亚型基因的相关性。脂质体转染质粒法获得内源性过表达IL-6的A2780细胞株和内源性抑制IL-6表达的CAOV-3细胞株。采用RT-PCR检测外源性和内源性IL-6作用于卵巢癌细胞后ERα和ERβ基因水平的变化,Western blot法检测上述ER亚型的蛋白水平。结果 TCGA数据库中高表达IL-6和ERα/ERβ卵巢癌的无进展生存率均低于各自的低表达者(P <0. 05)。IL-6基因与ERα基因呈显著正相关、与ERβ基因呈显著负相关(P <0. 01)。外源性及内源性过表达IL-6在A2780细胞中能上调ERα及下调ERβ的表达量,内源性抑制IL-6表达在CAOV-3细胞中则能下调ERα及上调ERβ的表达量,基因和蛋白表达相一致,ER亚型的变化程度对IL-6呈剂量依赖性。结论在卵巢癌细胞中IL-6能促进ERα并抑制ERβ的表达,提示IL-6可能通过调节ER亚型来参与卵巢癌的病程进展以及内分泌治疗耐药的形成。Objective To investigate effect of interleukin-6 （IL-6） on expression of estrogen receptor （ER） isoforms and to find correlation between IL-6 and ER with resistance mechanism of endocrine therapy for ovarian cancer. Methods A total of 535 samples of ovarian cancer were retrieved from the cancer genome atlas （TCGA） data base, and progression-free survival rates were compared among high and low expressions of IL-6 and ER isoforms to analyze correlation between total IL-6 gene with ER isoforms. A2780 cell strain of endogenous over-expressed IL-6 and CAOV-3 cell strain of endogenous inhibited IL-6 expression were obtained by liposomes transfected plasmid method. Changes of ERα and ERβ gene levels in ovarian cancer cells after affecting by ectogenesis and endogenous IL-6 were detected using reverse transcription polymerase chain reaction （RT-PCR）, and Western blot method was used to detect protein levels of the above ER isoforms. Results In TCGA database, progression-free survival rates of high-expressed IL-6 and ERα/ERβ were significantly lower than those of each low-expressed one respectively （ P 〈0.05）. IL-6 gene was positively correlated with ERα gene, while it was negatively correlated with ERβ gene （ P 〈0.01）. Ectogenesis and endogenous IL-6 over expressions in A2780 cells significantly up-regulated ERα expression and down-regulated ERβ expression. Endogenous inhibited IL-6 expression in CAOV-3 cells down-regulated ERα expression and up-regulated ERβ expression, and gene and protein expressions were uniform. Change degree of ER isoforms showed a dose-dependent manner with IL-6. Conclusion IL-6 may enhance ERα expression and inhibit ERβ expression in ovarian cancer cells, which indicates that IL-6 may involve in development of ovarian cancer and drug resistant formation of endocrine therapy by regulating ER isoforms.

关 键 词：卵巢癌 雌激素受体 白细胞介素-6 耐药性 

分 类 号：R737.31[医药卫生—肿瘤]