浙江大学学报（医学版）2026，Vol.55Issue(3)：256-266,11.DOI:10.3724/zdxbyxb-2025-0384
白头翁皂苷B4通过调控MAPK和Keap1/Nrf2信号通路介导的上皮-间充质转化抑制非小细胞肺癌转移
Anemoside B4 inhibits non-small cell lung cancer metastasis by modulating epithelial-mesenchymal transition mediated by the MAPK and Keap1/Nrf2 signaling pathways
摘要
Abstract
Objective:To investigate the effect and mechanism of Anemoside B4(AB4)on non-small cell lung cancer(NSCLC)metastasis.Methods:In vitro,the MTT assay was used to evaluate the effect of AB4 on the viability of human NSCLC cell lines A549 and H1975.Cell scratch and Transwell assays were performed to assess the effect of AB4 on the migration and invasion of A549 and H1975 cells induced by transforming growth factor-β1(TGF-β1).Western blotting and immunofluorescence were used to detect the expression of proteins related to epithelial-mesenchymal transition(EMT),the mitogen-activated protein kinase(MAPK)signaling pathway,and the oxidative stress signaling pathway.In vivo,a mouse model of melanoma lung metastasis was established by tail vein injection of B16-F10 cells to evaluate the effect of AB4(20,40 mg/kg)on melanoma lung metastasis.Blood routine parameters were measured,pathological changes in lung tissue were observed by hematoxylin and eosin staining,and the expression of EMT-,MAPK-,and oxidative stress signaling pathway-related proteins in lung tissue was analyzed by Western blotting.Results:In vitro,the MTT assay showed that AB4(5,10,20 µmol/L)had no cytotoxic effect.AB4 inhibited the migration and invasion of A549 and H1975 cells induced by TGF-β1;decreased the expression of N-cadherin,vimentin,Slug,and Snail while increasing E-cadherin expression in the EMT pathway;decreased Keap1 expression and increased Nrf2 expression in the oxidative stress pathway;and reduced the phosphorylation levels of JNK,ERK,and p38 in the MAPK pathway.In vivo,AB4 alleviated weight loss,inhibited melanoma lung metastasis,and the mechanism may be related to the inhibition of EMT,oxidative stress,and the MAPK signaling pathway in the lung tissue of model mice.Conclusions:AB4 inhibits tumor metastasis by modulating EMT mediated by the MAPK and Keap1/Nrf2 signaling pathways.关键词
非小细胞肺癌/肿瘤转移/白头翁皂苷B4/上皮-间充质转化/丝裂原活化蛋白激酶/氧化应激/小鼠Key words
Non-small cell lung cancer/Tumor metastasis/Anemoside B4/Epithelial-mesenchymal transition/Mitogen-activated protein kinase/Oxidative stress/Mice分类
医药卫生引用本文复制引用
苏倩,廖莲婷,刘丽娜,肖琳钰,沈余芳,杨世林,苑仁祎坤,高红伟..白头翁皂苷B4通过调控MAPK和Keap1/Nrf2信号通路介导的上皮-间充质转化抑制非小细胞肺癌转移[J].浙江大学学报（医学版）,2026,55(3):256-266,11.基金项目
广西自然科学基金(2025GXNSFAA069396) （2025GXNSFAA069396）
广西(青年)岐黄学者培养项目(GXQH202408) （青年）
广西科技计划(桂科AA23026010) （桂科AA23026010）
广西青年科技人才托举工程(GXYESS2025031)This study was supported by Guangxi Natural Science Foundation of China(2025GXNSF AA069396),Project of Guangxi Young Qihuang Scholar(GXQH202408),Guangxi Science and Technology Plan(GUIKEAA23026010),and Guangxi Young Elite Scientist Sponsorship Program(GXYESS2025031) （GXYESS2025031）
