辛伐他汀对TGF-β诱导的卵巢癌上皮间质转化的影响

doi:10.6040/j.issn.1671-7554.0.2018.171

摘要/Abstract

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EMT,可能通过调节SPAG9/JNK信号通路来发挥此作用。

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

Abstract: Objective To investigate the effects of simvastatin on epithelial-to-mesenchymal transition(EMT)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 EMT 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 EMT and TGF-β-induced EMT. 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 EMT induced by TGF-β in ovarian cancer cells, possibly by regulating SPAG9 / JNK pathway.

Key words: Ovarian cancer, Simvastatin, Transforming growth factor-β, Epithelial-to-mesenchymal transition, SPAG9/JNK pathway

中图分类号:

R737.31

何鹏娟,颜磊,范明君,刘祥斌,赵兴波. 辛伐他汀对TGF-β诱导的卵巢癌上皮间质转化的影响[J]. 山东大学学报 (医学版), 2018, 56(5): 46-51.

HE Pengjuan, YAN Lei, FAN Mingjun, LIU Xiangbin, ZHAO Xingbo. Effects of simvastatin on TGF-β induced epithelial-to-mesenchymal transition in ovarian cancer[J]. Journal of Shandong University (Health Sciences), 2018, 56(5): 46-51.

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