安徽医科大学学报2025,Vol.60Issue(11):2019-2025,7.DOI:10.19405/j.cnki.issn1000-1492.2025.11.005
芝麻素通过P53/SLC7A11/GPX4轴诱导三阴性乳腺癌细胞铁死亡
Sesamin induced ferroptosis in triple negative breast cancer cells through P53/SLC7A11/GPX4 pathway
摘要
Abstract
Objective To investigate the ferroptosis induced by sesamin in triple-negative breast cancer(TNBC)4T1 cells and its underlying mechanism.Methods The binding energy of sesamin with glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and P53 was analyzed by molecular docking.Mouse TNBC cell line 4T1 was used as a model.Different concentrations of sesamin were administered to 4T1 cells.The effect of sesamin on cell viability was assessed using the cell counting kit 8(CCK-8).Transwell assay was used to evaluate the effect of sesamin on cell migration and invasion.The contents of Fe2+,malondialdehyde(MDA),and reduced glutathione(GSH)in the cells were measured using kits.2′,7′-dichlorofluorescein diacetate(DCFH-DA)probe was employed to detect the content of reactive oxygen species(ROS)in cells.Real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)and Western blot were performed to evaluate the expression of GPX4,SLC7A11,and P53 at mRNA and protein levels.Results The binding energies of sesamin with GPX4,SLC7A11 and P53 were-21.46,-21.67,and-27.03 kJ/mol,respectively.Compared with the control group,the viability of 4T1 cells in different concentrations of sesamin groups decreased gradually(P<0.001),and the migration and invasion ability of 4T1 cells in 20,40,and 80 μmol/L sesamin groups decreased gradually(all P<0.001).Compared with the control group,the contents of Fe2+,MDA,and ROS in 4T1 cells of 20,40,and 80 μmol/L sesamin groups increased,and the content of GSH decreased.Compared with the control group,the mRNA and protein expression of GPX4 and SLC7A11 in 4T1 cells in the sesamin treatment group decreased,and the mRNA and protein expression of P53 increased(all P<0.001).Conclusion Sesamin may induce the ferroptosis in 4T1 cells through P53/SLC7A11/GPX4 pathway.关键词
芝麻素/铁死亡/分子对接/三阴性乳腺癌/P53/SLC7A11/GPX4Key words
sesamin/ferroptosis/molecular docking/triple negative breast cancer/P53/SLC7A11/GPX4分类
医药卫生引用本文复制引用
朱明美,于宛鹭,徐红月,崔新华,彭丹萍,于录..芝麻素通过P53/SLC7A11/GPX4轴诱导三阴性乳腺癌细胞铁死亡[J].安徽医科大学学报,2025,60(11):2019-2025,7.基金项目
国家自然科学基金(编号:32473029) National Natural Science Foundation of China(No.32473029) (编号:32473029)