中医药学报2025，Vol.53Issue(9)：26-32,7.DOI:10.19664/j.cnki.1002-2392.250182
木犀草素调控Wnt/β-catenin轴对肝癌细胞迁移和侵袭的影响
Effect of Luteolin on Migration and Invasion of Hepatocellular Carcinoma Cells by Regulating Wnt/β-catenin Axis
摘要
Abstract
Objective:To observe the effect of luteolin on migration and invasion of hepatocellular carcinoma(HCC)cells MHCC97H and Huh7,and explore its regulatory mechanism through Wnt/β-catenin signaling pathway.Methods:HCC cells were treated with luteolin for 24 h.Cell migration and invasion abilities were detected by scratch wound healing assay and Transwell invasion assay.Western blot and RT-PCR were used to measure the expression of migration-and invasion-related proteins/genes(ICAM-1,RHOC,MMP2,MMP9)and key components of Wnt/β-catenin pathway(Wnt1,β-catenin,GSK3β).A liver-lung metastasis model was established by tail vein injection of HCC cells in BABL/C nude mice.HE staining was performed to observe pathological changes and metastatic foci in liver and lung tissues.RT-PCR was used to detect the expression of Wnt/β-catenin pathway and migration/invasion-related genes.Results:Compared with control group,luteolin inhibited MHCC97H and Huh7 cell proliferation,significantly slowed wound healing process,reduced cell invasion number,and decreased expression levels of MMP2,ICAM-1,RHOC,Wnt1,β-catenin and GSK3β(P<0.05,P<0.01),while showing no significant effect on MMP-9 expression(P>0.05).In vivo experiments showed that morphological examination of liver and lung tissues revealed obvious tumor cell proliferation with diffuse dense arrangement and varying mitotic activity in model group,while luteolin group exhibited significant cell necrosis and apoptosis with markedly reduced number of liver/lung metastatic foci(P<0.05).Luteolin significantly decreased the expression levels of MMP2,ICAM-1,Wnt1,β-catenin and GSK3β in liver tissues(P<0.01),with no significant effect on MMP-9 expression(P>0.05).Conclusion:Luteolin can inhibit the expression of migration-and invasion-related ICAM-1,RHOC and MMP2 in HCC cell lines both in vitro and in vivo,and reduce the expression of Wnt,β-catenin and GSK3β in HCC.These results suggest that inhibition of Wnt/β-catenin signaling pathway activation may be one of the important mechanisms by which luteolin regulates HCC migration and invasion.关键词
木犀草素/迁移/侵袭/Wnt/β-catenin/作用机制Key words
Luteolin/Migration/Invasion/Wnt/β-catenin/Mechanism of action分类
医药卫生引用本文复制引用
杨培伟,马素平,刘光伟,陈欣菊,赵文霞..木犀草素调控Wnt/β-catenin轴对肝癌细胞迁移和侵袭的影响[J].中医药学报,2025,53(9):26-32,7.基金项目
国家自然科学基金项目(82003994) （82003994）
中国博士后科学基金第71批面上资助项目(2022M711082) （2022M711082）
河南省中医药科学研究专项课题(2019JDZX2034,2024ZY3011) （2019JDZX2034,2024ZY3011）
