现代检验医学杂志2025，Vol.40Issue(5)：16-21,6.DOI:10.3969/j.issn.1671-7414.2025.05.004
秦皮素调控TLR4/STAT3信号通路抑制卵巢癌细胞增殖、迁移和侵袭的机制研究
Mechanism of Fraxetin Regulating TLR4/STAT3 Signaling Pathway to Inhibit Proliferation,Migration and Invasion of Ovarian Cancer Cells
摘要
Abstract
Objective To investigate the effect of fraxetin(FXT)on the malignant biological behavior of ovarian cancer cells by regulating Toll-like receptor 4(TLR4)/signal transducer and activator of transcription 3(STAT3)pathway.Methods Ovarian cancer cell lines SKOV3 and SW626 and ovarian epithelial cell line IOSE80 were treated with different concentrations of FXT(0,10,20,40,60,80 and 100 μmol/L),and the cytotoxicity of FXT was detected by methylthiazolyl diphenyl-tetrazolium bromide(MTT)assay.SKOV3 and SW626 cells were randomly divided into control group,FXT low,medium,high dose(40,60,80 μmol/L)group and FXT(80 μmol/L)+colivelin(STAT3 agonist,0.5 μmol/L)group.Colony formation assay and Transwell assay were used to detect cell proliferation,invasion and migration.The expressions of epithelial-mesenchymal transition and TLR4/STAT3 pathway related proteins were measured by Western blot.Results Compared with IOSE80 cells,SKOV3 and SW626 cell survival gradually decreased with increasing FXT concentration,and the differences were statistically significant(F=134.283,146.831,P<0.001).Compared with the control group,the relative colony lineage rates of SKOV3 and SW626 cells in the FXT low-,medium-and high-dose groups,invasion rate and mobility were reduced(t=4.433～45.909),E-cadherin were increased(t=5.879～17.345),and the expression of N-cadherin,zinc finger transcription factors(snail),vimentin,TLR4,phosphorylated(p)-STAT3/STAT3,cell cycle protein D1(Cyclin D1)and MYC oncogenes(Cancer-myc,C-myc)expression were sequentially reduced(t=7.348～50.117),and the differences were statistically significant(all P<0.01),respectively.Compared with the high-dose FXT group,the relative colony formation rate,cell invasion rate and migration rate of SKOV3 and SW626 cells in the FXT+colivelin group increased(t=9.224～20.703),while the expression of E-cadherin protein decreased(t=3.104,5.041),the expression of N-cadherin,snail,vimentin,TLR4,p-STAT3/STAT3,Cyclin D1,and C-myc increased(t=8.403～42.175),and the differences were statistically significant(all P<0.05),respectively.Conclusion FXT may exert antitumor effects by antagonizing the activation of TLR4/STAT3 signaling pathway and inhibiting ovarian cancer cell proliferation,migration,invasion and epithelial mesenchymal transition.关键词
卵巢癌/秦皮素/Toll样受体4/信号转导和转录活化因子3通路/上皮间充质转化Key words
ovarian cancer/fraxetin/Toll-like receptor 4/signal transducer and activator of transcription 3 pathway/epithelial mesenchymal transition分类
医药卫生引用本文复制引用
安然,李茜,陆一菱,赖海燕,雷紫琴..秦皮素调控TLR4/STAT3信号通路抑制卵巢癌细胞增殖、迁移和侵袭的机制研究[J].现代检验医学杂志,2025,40(5):16-21,6.基金项目
四川省卫生健康委科研课题(19PJ013). （19PJ013）
