辛伐他汀对TGF-β诱导的卵巢癌上皮间质转化的影响  

Effects of simvastatin on TGF-β induced epithelial-to-mesenchymal transition in ovarian cancer

作　　者：何鹏娟 颜磊 范明君[1] 刘祥斌 赵兴波[1] HE Pengjuan1 , YAN Lei2, FAN Mingjun1 , LIU Xiangbin1 , ZHAO Xingbo1(1. Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affilicated to Shandong University; 2. Department of Gynecology, Hospital for Reproductive Medicine Affiliated to Shandong University, Jinan 250021, Shandong, Chin)

机构地区：[1]山东大学附属省立医院妇产科 [2]山东大学附属生殖医院妇科,山东济南250021

出　　处：《山东大学学报（医学版）》2018年第5期46-51,57,共7页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81272858;81202057)

摘　　要：目的探讨辛伐他汀对转化生长因子-β(TGF-β)诱导的卵巢癌细胞(Skvo3、A2780细胞)上皮间质转化(EMT)的影响。方法采用CCK-8法检测不同浓度辛伐他汀及TGF-β对卵巢癌细胞增殖的影响,并根据浓度结果将实验组分为对照组、辛伐他汀组、TGF-β组、辛伐他汀+TGF-β组,检测各组细胞增殖的变化;应用划痕实验检测各组细胞迁移能力;采用Transwell侵袭实验分析各组细胞侵袭能力;应用Western blotting测定各组细胞EMT及信号通路的变化。结果在Skvo3、A2780细胞中,辛伐他汀减少细胞增殖及TGF-β促进的细胞增殖,降低细胞迁移和侵袭及TGF-β诱导的细胞迁移和侵袭的增加,并逆转两种细胞的EMT及TGF-β诱导的EMT,进一步研究结果显示,辛伐他汀可降低两种细胞中精子相关抗原9(SPAG9)/c-Jun氨基末端激酶(JNK)通路的表达,而TGF-β促进SPAG9/JNK通路表达,且辛伐他汀减弱TGF-β对此通路的促进作用(P<0.05)。结论辛伐他汀减少TGF-β诱导的卵巢癌细胞增殖、迁移、侵袭和EM T,可能通过调节SPAG9/JNK信号通路来发挥此作用。Objective To investigate the effects of simvastatin on epithelial-to-mesenchymal transition（EM T） induced by transforming growth factor-β（TGF-β） in ovarian cancer cells（Skvo3 and A2780）. Methods The ovarian cancer cells were divided into the control group,simvastatin group,TGF-β group,and simvastatin＋TGF-β group. The effects of simvastatin and TGF-β at different concentrations on the cell proliferation were detected with CCK-8. The migration and invasion ability were assessed with wound healing assay and Transwell assay respectively. The changes of EM T and signaling pathway were determined with Western blotting. Results In Skvo3 and A2780 cells,simvastatin reduced cell proliferation and TGF-β-promoted cell proliferation,decreased cell migration and invasion,and reduced TGF-β-induced cell migration and invasion,and reversed EM T and TGF-β-induced EM T. Further experiments showed that simvastatin could reduce the expression of sperm-associated antigen 9（SPAG9）/c-Jun N-terminal kinase（JNK） pathway and reverse TGF-β-induced SPAG9/JNK pathway（P〈0.05）. Conclusion Simvastatin can reduce the proliferation,migration,invasion and EM T induced by TGF-β in ovarian cancer cells,possibly by regulating SPAG9/JNK pathway.

关 键 词：卵巢癌 辛伐他汀 转化生长因子-Β 上皮间质转化 SPAG9/JNK信号通路 

分 类 号：R737.31[医药卫生—肿瘤]