湖南中医药大学学报2025，Vol.45Issue(3)：445-452,8.DOI:10.3969/j.issn.1674-070X.2025.03.008
基于Nrf2/GPX4介导的铁死亡探讨异荭草素对非小细胞肺癌细胞增殖和凋亡的影响
Effects of isoorientin on proliferation and apoptosis of non-small cell lung cancer cells based on Nrf2/GPX4-mediated ferroptosis
摘要
Abstract
Objective To investigate the effects of isoorientin(ISO)on the malignant biological phenotypes of non-small cell lung cancer(NSCLC)cells based on the nuclear factor-erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)signaling pathway.Methods Human NSCLC cells HCC827 were used as the research object.Control group,ISO+oe-NC group,ISO+oe-Nrf2 group,oe-Nrf2 group,and oe-NC group were divided in the experiment.Cell viability was measured by MTT assay,cell proliferation was checked by Edu assay,cell apoptosis and lipid peroxidation levels were identified by flow cytometry,levels of malondialdehyde(MDA),iron,reduced glutathione(GSH)/oxidized glutathione(GSSG)in cells were measured by kits,expression levels of Nrf2(nuclear),GPX4,prostaglandin-endoperoxide synthase 2(PTGS2),and solute carrier family 7 member 11(SLC7A11)proteins in cells were measured by Western blot,and Nrf2 nuclear translocation was examined by immunofluorescence assay.Results Compared with the oe-NC group,the isoorientin+oe-NC group had significantly decreased number of Edu-positive cells(P<0.05),significantly higher apoptosis rate(P<0.05),the significantly higher levels of lipid peroxidation,MDA,and iron in cells(P<0.05),the significantly lower GSH/GSSG level in cells(P<0.05),the significantly reduced expression of Nrf2(nuclear),GPX4,and SLC7A11 proteins in cells(P<0.05),the significantly up-regulated PTGS2 protein expression level(P<0.05),and reduced Nrf2 nuclear translocation;compared with the ISO+oe-NC group,the ISO+oe-Nrf2 group showed significantly increased Edu positive cells(P<0.05),the significantly decreased apoptosis rate(P<0.05),the significantly decreased levels of lipid peroxidation,MDA,and iron in cells(P<0.05),the significantly increased GSH/GSSG level in cells(P<0.05),the significantly up-regulated expression of Nrf2(nuclear),GPX4,and SLC7A11 proteins in cells(P<0.05),the significantly down-regulated expression of PTGS2 protein(P<0.05),and increased Nrf2 nuclear translocation.Conclusion ISO can inhibit the proliferation of NSCLC cells and promote their apoptosis,and the mechanism involved may be related to the induction of ferroptosis by inhibiting the Nrf2/GPX4 signaling pathway.关键词
非小细胞肺癌/异荭草素/Nrf2/GPX4/铁死亡/增殖/凋亡Key words
non-small cell lung cancer/isoorientin/Nrf2/GPX4/ferroptosis/proliferation/apoptosis分类
医药卫生引用本文复制引用
江小红,库雄,魏从兵..基于Nrf2/GPX4介导的铁死亡探讨异荭草素对非小细胞肺癌细胞增殖和凋亡的影响[J].湖南中医药大学学报,2025,45(3):445-452,8.基金项目
湖北省中医药管理局中医药科研项目(ZY2023F053) （ZY2023F053）
武汉市中医药科研项目(WZ24Q13). （WZ24Q13）
