Ferroptosis inducer Erastin inhibits proliferation of liver cancer cells in vitro by down-regulating ACSL4
10.12122/j.issn.1673-4254.2024.11.09
- VernacularTitle:铁死亡诱导剂Erastin下调ACSL4抑制肝癌细胞体外增殖
- Author:
Peipei ZHAO
1
;
Zhigang ZHOU
;
Yuanyuan YANG
;
Shusheng HUANG
;
Yixuan TU
;
Jian TU
Author Information
1. 桂林医学院药学院,广西 桂林 541199;广西肝脏损伤与修复分子医学重点实验室,广西 桂林 541199
- Keywords:
liver cancer;
cell proliferation;
Erastin;
Acyl-CoA synthetase long-chain family member 4;
ferroptosis
- From:
Journal of Southern Medical University
2024;44(11):2131-2136
- CountryChina
- Language:Chinese
-
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.
