芒柄花素调控miR-19b-3p/TGF-β/Smad2信号通路影响卵巢癌细胞的增殖、迁移、侵袭和凋亡  

Formononetin affects the proliferation,migration,invasion and apoptosis of ovarian cancer cells by regulating the miR-19b-3p/TGF-β/Smad2 signaling pathway

作　　者：牛永莉[1] 贾晓波[1] 王艳[1] NIU Yongli;JIA Xiaobo;WANG Yan(Jiuquan People's Hospital,Jiuquan 73500,China)

机构地区：[1]酒泉市人民医院,甘肃酒泉735000

出　　处：《沈阳药科大学学报》2021年第10期1068-1075,共8页Journal of Shenyang Pharmaceutical University

摘　　要：目的研究芒柄花素对卵巢癌细胞增殖、迁移侵袭、凋亡的影响,并分析其机制是否与调控miR-19b-3p/转化生长因子-β(transforming growth factor-beta,TGF-β)/Smad2信号通路相关。方法采用噻唑蓝法、transwell实验、流式细胞术分析不同浓度(35、70、140μmol·L^(-1))的芒柄花素对卵巢癌细胞SKOV3增殖活力、迁移侵袭和凋亡的影响。实时定量PCR分析miR-19b-3p表达。采用上述方法检测过表达或抑制miR-19b-3p对SKOV3增殖活力、迁移侵袭和凋亡的影响。免疫印迹法检测TGF-β和Smad2蛋白表达量。结果35、70、140μmol·L^(-1)的芒柄花素处理显著抑制SKOV3细胞活力,减少迁移和侵袭数量,增加细胞凋亡率,下调miR-19b-3p表达。过表达miR-19b-3p显著增加SKOV3细胞活力、迁移和侵袭数量,降低细胞凋亡率,上调TGF-β和Smad2蛋白表达量。抑制miR-19b-3p表达显著抑制SKOV3细胞活力,减少迁移和侵袭数量,增加细胞凋亡率,下调TGF-β和Smad2蛋白表达量。140μmol·L^(-1)的芒柄花素显著抑制TGF-β和Smad2蛋白表达量。过表达miR-19b-3p可显著减弱芒柄花素处理对SKOV3细胞增殖、迁移侵袭、凋亡以及TGF-β和Smad2蛋白表达的影响。结论芒柄花素可抑制卵巢癌细胞SKOV3增殖、迁移和侵袭,诱导细胞凋亡,其抗肿瘤作用可能与调控miR-19b-3p/TGF-β/Smad2信号通路有关。Objective To study the effects of formononetin on the proliferation,migration,invasion and apoptosis of ovarian cancer cells,and further to analyze whether its mechanism is related to the regulation of miR-19b-3p/transforming growth factor-β(TGF-β)/Smad2 signaling pathway.Methods The effects of formononetin at different concentrations(35,70 and 140μmol·L^(-1))on the proliferation,migration,invasion and apoptosis of ovarian cancer cell SKOV3 were analyzed by the thiazole blue(MTT)method,transwell experiment,and flow cytometry,respectively.Expression of miR-19b-3p was conducted by realtime quantitative PCR(RT-qPCR).The effects of miR-19b-3p overexpression or inhibition on the proliferation,migration,invasion and apoptosis of SKOV3 were detected by the above methods.Western blotting was applied to calculate the expression of TGF-βand Smad2 proteins.Results Treated with 35,70,and 140μmol·L^(-1)formononetin significantly inhibited SKOV3 cell viability,decreased the number of cell migration and invasion,increased cell apoptosis rate,and down-regulated the expression of miR-19b-3p.The overexpression of miR-19b-3p significantly increased cell viability,migration and invasion cell numbers,decreased cell apoptosis rate,and up-regulated the expression of TGF-βand Smad2 proteins.miR-19b-3p inhibition significantly decreased cell viability,migration and invasion cell numbers,increased cell apoptosis rate,and down-regulated the expression of TGF-βand Smad2 proteins.140μmol·L^(-1)formononetin significantly inhibited TGF-βand Smad2 protein expression.The miR-19b-3p overexpression significantly reduced the effects of formononetin treatment on the proliferation,migration,invasion,apoptosis,and TGF-βand Smad2 protein expression of SKOV3 cells(P<0.05).Conclusion Formononetin can inhibit the proliferation,migration and invasion,and induce cell apoptosis of ovarian cancer cells SKOV3.Its anti-tumor effect may be related to the regulation of miR-19b-3p/TGF-β/Smad2 signaling pathway.

关 键 词：芒柄花素 卵巢癌 细胞增殖 迁移侵袭 凋亡 miR-19b-3p TGF-β/Smad2 

分 类 号：R96[医药卫生—药理学] R28[医药卫生—药学]