南方医科大学学报2024,Vol.44Issue(11):2131-2136,6.DOI:10.12122/j.issn.1673-4254.2024.11.09
铁死亡诱导剂Erastin下调ACSL4抑制肝癌细胞体外增殖
Ferroptosis inducer Erastin inhibits proliferation of liver cancer cells in vitro by down-regulating ACSL4
摘要
Abstract
Objective To investigate the expression of Acyl-CoA synthetase long-chain family member 4(ACSL4)in liver cancer and its role in regulating ferroptosis and proliferation of liver cancer cells.Methods Clinical samples of liver cancer and adjacent normal liver tissues were examined for malondialdehyde(MDA)contents and for expressions of mRNA and protein expressions of ACSL4 and proliferating cell nuclear antigen(PCNA)using RT-qPCR and Western blotting.Human liver cancer Huh-7 cells were treated with Erastin(a ferroptosis inducer),Fer-1(a ferroptosis inhibitor),or both,and the changes in expression levels of MDA,ACSL4 and PCNA were detected,and the cell proliferation was assessed with plate cloning assay.Results MDA contents were lower and ACSL4 and PCNA expressions were higher significantly in liver cancer tissues than in adjacent liver tissues.In Huh-7 cells,Erastin treatment significantly inhibited mRNA and protein expressions of ACSL4 and PCNA,suppressed cell proliferation,and increased MDA contents.Fer-1 alone did not produce significant effect on cell viability but reversed the effect of Erastin on ACSL4 and PCNA expressions,cell proliferation and MDA contents.Conclusion ACSL4 level is significantly overexpressed in liver cancer.Erastin increases MDA contents and down-regulates ACSL4 expression,thereby promoting ferroptosis and inhibiting proliferation of liver cancer cells,and these effects can be reversed by Fer-1.关键词
肝癌/细胞增殖/Erastin/ACSL4/铁死亡Key words
liver cancer/cell proliferation/Erastin/Acyl-CoA synthetase long-chain family member 4/ferroptosis引用本文复制引用
赵培培,周志刚,杨媛媛,黄树升,涂逸轩,涂剑..铁死亡诱导剂Erastin下调ACSL4抑制肝癌细胞体外增殖[J].南方医科大学学报,2024,44(11):2131-2136,6.基金项目
国家自然科学基金(82060662) (82060662)
广西区自然科学基金(2022JJA140776,2022JJA140639)Supported by National Natural Science Foundation of China(82060662). (2022JJA140776,2022JJA140639)