Mechanism of Fraxetin Regulating TLR4/STAT3 Signaling Pathway to Inhibit Proliferation,Migration and Invasion of Ovarian Cancer Cells
10.3969/j.issn.1671-7414.2025.05.004
- VernacularTitle: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
- Author:
Ran AN
1
;
Qian LI
1
;
Yiling LU
1
;
Haiyan LAI
1
;
Ziqin LEI
1
Author Information
1. 成都市第三人民医院,西南交通大学附属医院药学部,成都 610031
- Publication Type:Journal Article
- Keywords:
ovarian cancer;
fraxetin;
Toll-like receptor 4/signal transducer and activator of transcription 3 pathway;
epithelial mesenchymal transition
- From:
Journal of Modern Laboratory Medicine
2025;40(5):16-21
- CountryChina
- Language:Chinese
-
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.
