中国中医药信息杂志2024，Vol.31Issue(9)：124-130,7.DOI:10.19879/j.cnki.1005-5304.202403742
大叶茜草素对肝癌细胞铁死亡的影响及作用机制研究
Study on Effects and Mechanism of Mollugin in Ferroptosis in Hepatocellular Carcinoma Cells
摘要
Abstract
Objective To investigate the mechanism of inhibitory effect of mollugin on hepatocellular carcinoma based on the ferroptosis pathway.Methods HepG2 cells were cultured in vitro and divided into control group,mollugin low-(10 μmol/L),medium-(20 μmol/L),and high-dosage(40 μmol/L)groups based on the inhibitory concentration of 50%.The cell viability was detected by CCK-8 method,cytotoxicity was detected by LDH kit,and the ability of cell colony formation was observed by clone formation assay,the contents of GSH,MDA,ROS,SOD,superoxide,lipid peroxide and MMP were detected,the protein expression of ferroptosis suppressor protein 1(FSP1),GTP cyclohydrolase 1(GCH1),dihydroorotate dehydrogenase(DHODH)and glutathione peroxidase 4(GPX4)were detected by Western blot,the mRNA expression of FSP1,DHODH,GCH1 and GPX4 were detected using RT-qPCR.The effect of mollugin on cell viability and GSH,MDA contents of hepatocellular carcinoma cells were observed under overexpression and silencing of GPX4 by mollugin.Results The medium-and high-dose of mollugin could reduce the number of clone formation in HepG2 cells,decrease the GSH content and SOD activity of cells,increase the content of MDA,superoxide,lipid peroxides and ROS,and decreased MMP(P<0.001).The intervention of mollugin had no significant effect on the expressions of FSP1,GCH1,DHODH protein and mRNA in HepG2 cells,but could decrease the expression of GPX4 protein and mRNA(P<0.001).Overexpression and silencing experiments confirmed that GPX4 was the core target for the regulation of ferroptosis by mollugin.Conclusion Mollugin mainly exerts its anti-liver cancer effect by regulating GPX4 mediated ferroptosis.关键词
大叶茜草素/肝细胞癌/铁死亡/HepG2细胞/谷胱甘肽过氧化物酶4Key words
mollugin/hepatocellular carcinoma/ferroptosis/HepG2 cells/GPX4分类
医药卫生引用本文复制引用
姜宇朗,余永鑫,王子元,潘子扬,孙明瑜..大叶茜草素对肝癌细胞铁死亡的影响及作用机制研究[J].中国中医药信息杂志,2024,31(9):124-130,7.基金项目
国家自然科学基金(82374188) （82374188）
山东省重点研发计划(2021CXGC010509) （2021CXGC010509）
国家中医药管理局慢性肝病虚损重点研究室和上海市中医临床重点实验室(20DZ2272200) （20DZ2272200）
