Actinomycin D inhibits liver cancer invasion and metastasis by suppressing the Wnt/β-catenin signaling pathway and epithelial-mesenchymal transition  

作　　者：SUN Yitong LI Congyao LIANG Chen LU Qiuyan WU Yude 孙伊彤;李聪瑶;梁晨;路秋艳;吴玉德

机构地区：[1]College of Biology and Agriculture,Jiamusi University,Jiamusi 15400,China.

出　　处：《World Journal of Integrated Traditional and Western Medicine》2024年第4期142-149,共8页世界中西医结合杂志(英文)

基　　金：supported by the Heilongjiang Province College Student Innovation and Entrepreneurship Training Program(No.202310222032).

摘　　要：Objective:To investigate actinomycin D’s effects on liver cancer progression,explore its underlying mechanisms,focusing on epithelial-mesenchymal transition(EMT)and Wnt/β-catenin signaling,offer new insights and references for identifying low toxicity traditional Chinese medicine(TCM)monomers with the same targets but lower toxicity or developing compound formulations to enhance pathway blocking effects,and to innovate and develop integrated Chinese and western medicine treatment strategies.Methods:Human liver cancer cells(HepG2)were treated with actinomycin D for in vitro assays.Cell proliferation was assessed via CCK-8,while transwell assays evaluated invasion and migration.Western blot analyzed expression of EMT markers(E-cadherin,β-catenin,Twist1).A nude mouse metastatic model using HepG2 cells was established for in vivo validation,with metastasis efficiency and molecular markers compared between treatment and control groups.Results:Actinomycin D suppressed liver cancer cell proliferation in a dose-dependent and time-dependent manner(CCK-8 assay)and inhibited cell invasion and migration(assessed by transwell assay).Western blot analysis showed that actinomycin D downregulatedβ-catenin and Twist1 while upregulating E-cadherin,indicating suppression of EMT.In vivo experiments demonstrated that actinomycin D significantly reduced metastatic efficiency in mice,consistent with decreasedβ-catenin/Twist1 expression and increased E-cadherin levels in tumor tissues.Conclusions:Actinomycin D suppresses liver cancer invasion and metastasis by inhibiting theWnt/β-catenin pathway and EMTprogression.These findings highlight its dual antitumor role in both proliferation inhibition and metastasis suppression,providing mechanistic insights for its clinical applications.

关 键 词：Liver cancer Actinomycin D WNT/Β-CATENIN Epithelial-mesenchymal transition(EMT) Tumor invasion and metastasis Traditional Chinese medicine(TCM) 

分 类 号：R285[医药卫生—中药学]