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OA
Anemoside B4 inhibits non-small cell lung cancer metastasis by modulating epithelial-mesenchymal transition mediated by the MAPK and Keap1/Nrf2 signaling pathways
目的:探讨白头翁皂苷B4(AB4)对非小细胞肺癌转移的影响及作用机制.方法:体外实验采用MTT法检测AB4对人非小细胞肺癌细胞A549和H1975活性的影响;细胞划痕和Transwell实验检测AB4对转化生长因子-β1(TGF-β1)诱导的A549和H1975细胞迁移及侵袭能力的影响;蛋白质印迹法及免疫荧光法检测上皮-间充质转化(EMT)、丝裂原活化蛋白激酶(MAPK)和氧化应激信号通路相关蛋白的表达.体内实验通过尾静脉注射B16-F10细胞建立C57BL/6J小鼠皮肤黑色素瘤肺转移模型,用AB4(20、40 mg/kg)干预后检测模型鼠血常规指标、苏木精-伊红染色观察肺组织病理变化、蛋白质印迹法检测肺组织EMT、MAPK和氧化应激信号通路相关蛋白表达.结果:在体外实验中,AB4(5、10、20 µmol/L)无细胞毒性,但其可抑制TGF-β1诱导的A549和H1975细胞迁移及侵袭,下调EMT信号通路中神经钙黏素、波形蛋白、Slug和Snail表达,上调上皮钙黏素表达,也可下调氧化应激信号通路中Keap1表达,上调Nrf2表达,还能够降低MAPK信号通路中磷酸化JNK、磷酸化ERK、磷酸化p38表达水平.在体内实验中,AB4可减少肺转移模型鼠体重下降,抑制黑色素瘤肺转移,机制可能与抑制模型鼠肺组织中EMT、氧化应激和MAPK信号通路有关.结论:AB4通过调控MAPK信号通路和Keap1/Nrf2氧化应激介导的EMT,抑制肿瘤转移.
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.
苏倩;廖莲婷;刘丽娜;肖琳钰;沈余芳;杨世林;苑仁祎坤;高红伟
广西中医药大学中医药壮瑶医药研究院,广西 南宁 530200||广西中医药大学药学院,广西 南宁 530200广西中医药大学中医药壮瑶医药研究院,广西 南宁 530200||广西中医药大学药学院,广西 南宁 530200广西中医药大学中医药壮瑶医药研究院,广西 南宁 530200||广西中医药大学药学院,广西 南宁 530200广西中医药大学中医药壮瑶医药研究院,广西 南宁 530200||广西中医药大学药学院,广西 南宁 530200广西中医药大学中医药壮瑶医药研究院,广西 南宁 530200||广西中医药大学药学院,广西 南宁 530200广西中医药大学中医药壮瑶医药研究院,广西 南宁 530200||广西中医药大学药学院,广西 南宁 530200广西中医药大学中医药壮瑶医药研究院,广西 南宁 530200||广西中医药大学药学院,广西 南宁 530200广西中医药大学中医药壮瑶医药研究院,广西 南宁 530200||广西中医药大学药学院,广西 南宁 530200
医药卫生
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
Non-small cell lung cancerTumor metastasisAnemoside B4Epithelial-mesenchymal transitionMitogen-activated protein kinaseOxidative stressMice
《浙江大学学报（医学版）》 2026 (3)
256-266,11
广西自然科学基金(2025GXNSFAA069396)广西(青年)岐黄学者培养项目(GXQH202408)广西科技计划(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)
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