亚硒酸钠通过活性氧(ROS)/谷胱甘肽(GSH)/谷胱甘肽过氧化物酶(GPX4)轴诱导非小细胞肺癌A549细胞铁死亡

硒作为人体必需的微量元素，具有抗癌作用，但其抗癌机制尚不明确，因此，通过探讨亚硒酸钠是否可以通过铁死亡途径抑制肺癌A549细胞增殖及其肺癌A549细胞发生铁死亡的具体机制。通过细胞增殖实验(CCK-8实验)及细胞计数实验评价亚硒酸钠对A549细胞增殖的影响，通过流式细胞术分析亚硒酸钠对肺癌A549细胞内线粒体膜电位(MMP)及活性氧(ROS)水平的影响，通过亚铁离子检测试剂盒检测亚硒酸钠作用后肺癌A549细胞内亚铁离子含量变化，MDA检测试剂盒分析亚硒酸钠作用后肺癌A549细胞内脂质氧化产物丙二醛(MDA)含量，分光光度法分析亚硒酸钠对肺癌A549细胞内谷胱甘肽过氧化物酶4(GPX4)及谷胱甘肽(GSH)的表达影响。研究发现：亚硒酸钠能够显著抑制肺癌A549细胞增殖，且亚硒酸钠抑制肺癌A549细胞的半数抑制率(IC₅₀)为10μmol/L;亚硒酸钠能诱导肺癌A549细胞内ROS过度积累并使细胞内谷胱甘肽耗竭；亚硒酸钠作用后，细胞内线粒体膜电位水平显著降低，MDA含量升高而GPX4蛋白表达下调。研究表明，亚硒酸钠能通过诱导肺癌A549细胞内ROS过度积累，引起细胞内...

Sodium Selenite Induces Ferroptosis in Non-small Cell Lung Cancer A549 Cells Via Reactive Oxygen Species (ROS)/Glutathione (GSH)/Glutathione Peroxidase4 (GPx4) Axis

Abstract: This study mainly investigated the mechanism of sodium selenite induced iron death in non-small cell lung cancer A549 cells. Firstly, cell proliferation assay (CCK-8 assay) and cell counting assay were used to evaluate the effect of sodium selenite on A549 cell proliferation; The effects of sodium selenite on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels in A549 cells were analyzed by flow cytometry; The contents of ferrous ions and malondialdehyde (MDA), the product of lipid oxidation, in A549 cells after sodium selenite treatment were detected by kit; The effects of sodium selenite on the expression of glutathione peroxidase 4 (GPX4) and glutathione (GSH) in A549 cells were analyzed by spectrophotometry. Through the above study, it was found that sodium selenite could inhibit the proliferation of A549 cells, and the IC50 was 10 10 μmol/L; In addition, sodium selenite could induce ROS accumulation, reduce GSH and MMP levels, increase MDA levels, and downregulate GPX4 expression in A549 cells. Therefore, sodium selenite may cause massive depletion of GSH by increasing the ROS content in lung cancer A549 cells, resulting in decreased GPX4 expression and inducing iron death.