中国肿瘤生物治疗杂志2017，Vol.24Issue(6)：601-607,7.DOI:10.3872/j.issn.1007-385X.2017.06.005
IL-6经PI3K/Akt通路诱导卵巢癌细胞对他莫西芬耐药
IL-6 induces tamoxifen resistance in ovarian cancer cells through PI3K/Akt pathway
摘要
Abstract
Objective:This study aimed to explore the mechanism of tamoxifen (TAM) resistance caused by IL-6 in ovarian cancer cells.Methods:Human ovarian cancer A2780 cell line that endogenously over-expressing IL-6 and human ovarian cancer CAOV-3 cell line that exogenously depleting IL-6 were constructed;exogenous IL-6 (50 ng/ml) were used for pretreatment of A2780 cells (A2780/perIL-6 cells),and Western blotting was used to detect the effect of endogenous/exogenous IL-6 on the phosphorylation level of ERα Ser167 in ovarian cancer cells;IL-6 and/or Wortmannin (PI3K inhibitor) were used to treat A2780 cells and western blotting was used to detect their effect on the phosphorylation of Akt and ERα;MTT assay was used to detect the effect of Wortmannin and endogenous/exogenous IL-6 on the sensitivity of A2780 cells to TAM;luciferase reporter assay was performed to detect transcription activity of ERα in ovarian cancer cells,and to explore the possible signaling pathway.Results:Both exogenous and endogenous over-expression of IL-6 could obviously increase the level of ERα Ser167 phosphorylation in A2780 cells (all P ＜0.01),while endogenous depletion of IL-6 could reduce the level of ERα Ser167 phosphorylation in CAOV-3 cells (P ＜ 0.01).It also found that wortmannin (PI3 K inhibitor) could significantly antagonize IL-6-induced TAM resistance and phosphorylation of ERα Ser167.IL-6 promoted ERa transcription activity,while this activation was not blocked by the PI3K-specific inhibitor wortmannin.Conclusion:These results indicate that IL-6 could induce ERa phosphorylation by triggering PI3K/Akt signaling pathway to activate the ER pathway,and thereby induce the resistance of ovarian cancer cells to TAM.关键词
卵巢癌/白细胞介素-6/他莫西芬/耐药/雌激素受体/PI3K/Akt通路Key words
ovarian cancer/interleukin-6 (IL-6)/tamoxifen (TAM)/resistance/estrogen receptor (ER)/PI3K/Akt pathway分类
医药卫生引用本文复制引用
赵雅瑮,孙旸,黄素辉,杨静,王越,李玲,郭小芹,李艳秋..IL-6经PI3K/Akt通路诱导卵巢癌细胞对他莫西芬耐药[J].中国肿瘤生物治疗杂志,2017,24(6):601-607,7.基金项目
国家自然科学基金资助项目(No.81572852,No.81502256) （No.81572852,No.81502256）
天津市自然科学基金资助项目(No.12JCZDJC26300) （No.12JCZDJC26300）
武警后勤学院科学技术研究资助项目(No.2015ZXKF05,No.WHB201404,No.WHB201505).Project supported by the National Natural Science Foundation of China(No.81273520,No.81502256),the Great Program of the Science Foundation of Tianjin(No.12JCZDJC26300),and the Great Program for Science and Technology in Logistics College of Chinese People's Armed Police Forces (No.2015 ZXKF05,No.WHB201404,No.WHB201406) （No.2015ZXKF05,No.WHB201404,No.WHB201505）
