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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英文版,2025,45(3):445-452.[Click to copy
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| 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 |
| 江小红,库雄,魏从兵 |
| (中国地质大学(武汉)医院, 湖北 武汉 430070;武汉科技大学, 湖北 武汉 430070) |
| 摘要: |
| 目的 基于核因子E2相关因子2（Nrf2）/谷胱甘肽过氧化物酶4（GPX4）信号通路，探究异荭草素（ISO）对非小细胞肺癌（NSCLC）细胞恶性生物学表型的影响。方法 以人NSCLC细胞HCC827为研究对象，实验分为对照组、异荭草素+oe-NC组、异荭草素+oe-Nrf2组、oe-Nrf2组、oe-NC组。MTT检测细胞活力，Edu实验检测细胞增殖，流式细胞术检测细胞凋亡及脂质过氧化水平，试剂盒检测细胞中丙二醛（MDA）、铁、还原型谷胱甘肽（GSH）/氧化型谷胱甘肽（GSSG）水平，Western blot检测细胞中Nrf2（细胞核）、GPX4、前列腺素过氧化物合酶2（PTGS2）及溶质载体家族7成员11（SLC7A11）蛋白的表达水平，免疫荧光实验检测Nrf2核转位情况。结果 相对于oe-NC组，异荭草素+oe-NC组Edu阳性细胞数减少（P<0.05），细胞凋亡率增加（P<0.05），细胞中的脂质过氧化、MDA、铁水平升高（P<0.05），细胞中的GSH/GSSG水平降低（P<0.05），细胞中的Nrf2（细胞核）、GPX4、SLC7A11蛋白的表达下调（P<0.05），PTGS2蛋白的表达上调（P<0.05），Nrf2核转位减少；相对于异草红素+oe-NC组，异草红素+oe-Nrf2组Edu阳性细胞数增加（P<0.05），细胞凋亡率降低（P<0.05），细胞中的脂质过氧化、MDA、铁水平降低（P<0.05），细胞中的GSH/GSSG水平升高（P<0.05），细胞中的Nrf2（细胞核）、GPX4、SLC7A11蛋白的表达水平上调（P<0.05），PTGS2蛋白的表达水平下调（P<0.05），Nrf2核转位增加。结论 ISO能够抑制非小细胞肺癌细胞的增殖，并促进其凋亡，所涉及机制可能与抑制Nrf2/GPX4信号通路来诱导铁死亡有关。 |
| 关键词: 非小细胞肺癌 异荭草素 Nrf2/GPX4 铁死亡 增殖 凋亡 |
| DOI：10.3969/j.issn.1674-070X.2025.03.008 |
| Received:December 21, 2024 |
| 基金项目:湖北省中医药管理局中医药科研项目（ZY2023F053）；武汉市中医药科研项目（WZ24Q13）。 |
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| Effects of isoorientin on proliferation and apoptosis of non-small cell lung cancer cells based on Nrf2/GPX4-mediated ferroptosis |
| JIANG Xiaohong, KU Xiong, WEI Congbing |
| (Hospital of China University of Geosciences (Wuhan), Wuhan, Hubei 430070, China;Wuhan University of Science and Technology, Wuhan, Hubei 430070, China) |
| 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. |
| Key words: non-small cell lung cancer isoorientin Nrf2/GPX4 ferroptosis proliferation apoptosis |
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