中国病理生理杂志2024，Vol.40Issue(2)：282-290,9.DOI:10.3969/j.issn.1000-4718.2024.02.011
基于p53/SLC7A11/GPX4信号轴探讨七叶内酯诱导小鼠乳腺癌4T1细胞铁死亡的作用机制
Mechanism of esculetin promoting ferroptosis of mouse breast cancer 4T1 cells based on p53/SLC7A11/GPX4 axis
摘要
Abstract
AIM:To investigate the mechanism through which esculetin induces ferroptosis of mouse breast cancer 4T1 cells.METHODS:Molecular docking of esculetin with p53,solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)proteins was performed,and Kaplan-Meier curves and time-dependent receiver oper-ating characteristic curves were drawn.The 4T1 cells were divided into 6 groups,namely the control(CON),1/2 IC50,IC50,2 IC50,erastin,and capecitabine groups.The appropriate drug concentration for treating 4T1 cells was screened by CCK-8 assay.The invasion and migration abilities of 4T1 cells following esculetin treatment at the selected drug concentra-tion were analyzed by scratch test and Transwell assay.Mitochondrial morphological change were examined by electron mi-croscopy.The levels of ferroptotic cell death were then quantified by Fe2+,reactive oxygen species(ROS),malondialde-hyde(MDA),glutathione(GSH),and GPX4 assays.Western blot was performed to evaluate the protein levels of p53,SLC7A11,GPX4 and acyl-CoA synthetase long-chain family member 4(ACSL4).RESULTS:Compared with CON group,the esculetin 1/2 IC50,IC50 and 2 IC50 groups showed smaller size,increased membrane density,and decreased ridge of mitochodria,as well as decreased levels of GSH and GPX4,reduced cell invasion and migration abilities,and de-creased levels of SLC7A11 and GPX4 proteins(P＜0.05).Furthermore,these groups exhibited increased levels of Fe2+,ROS,and MDA,as well as elevated p53 and ACSL4 protein abundance(P＜0.05).CONCLUSION:Esculetin pro-motes ferroptosis of 4T1 cells through a mechanism involving the p53/SLC7A11/GPX4 regulatory axis.关键词
乳腺癌/七叶内酯/铁死亡/p53/SLC7A11/GPX4信号通路Key words
breast cancer/esculetin/ferroptosis/p53/SLC7A11/GPX4 signaling pathway分类
医药卫生引用本文复制引用
何丹,李琳霈,谭小宁,郜文辉,田雪飞,曾普华..基于p53/SLC7A11/GPX4信号轴探讨七叶内酯诱导小鼠乳腺癌4T1细胞铁死亡的作用机制[J].中国病理生理杂志,2024,40(2):282-290,9.基金项目
国家自然科学基金资助项目(No.82074425) （No.82074425）
国家中医药管理局青年岐黄学者人才项目 （）
湖南省科技拔尖领军人才项目 （）
湖南省卫生健康委高层次领军人才项目和中医药神农工程领军人才项目 （）
湖南省重点研发项目(No.2021SK2006) （No.2021SK2006）
湖南省自然基金资助项目(No.2021JJ30417) （No.2021JJ30417）
中国博士后科学基金第73批面上资助项目(No.2023M731069) （No.2023M731069）
湖南省中医药管理局项目(No.B2023086) （No.B2023086）
湖南省卫健委项目(No.20231748) （No.20231748）
