摘要
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(IC_(50))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GSH大量耗竭,导致GPX4表达下降,诱导细胞发生铁死亡。
As an essential trace element for human body,selenium has anticancer effect,but its anticancer mechanism is still unclear.Therefore,this study mainly discussed whether sodium selenite can inhibit the proliferation of lung cancer A549 cells through the ferroptosis pathway and the specific mechanism of ferroptosis of lung cancer A549 cells.Firstly,the effect of sodium selenite on the proliferation of A549 cells was evaluated by cell proliferation assay(CCK-8 assay)and cell counting assay;the effects of sodium selenite on mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)levels in lung cancer A549 cells were analyzed by flow cytometry;the changes of ferrous ion content in lung cancer A549 cells treated with sodium selenite were detected by ferrous ion detection kit;the content of malondialdehyde(MDA)was analyzed by MDA assay kit,which was the product of lipid oxidation in lung cancer A549 cells after sodium selenite treatment;the effects of sodium selenite on the expression of glutathione peroxidase 4(GPX4)and glutathione(GSH)in lung cancer A549 cells were analyzed by spectrophotometry.According to the above research,sodium selenite significantly inhibited the proliferation of lung cancer A549 cells,and the half inhibition rate(IC_(50))of sodium selenite on lung cancer A549 cells was 10μmol/L;in addition,studies have found that sodium selenite induced excessive accumulation of ROS and depletion of intracellular glutathione in lung cancer A549 cells;after sodium selenite treatment,the intracellular mitochondrial membrane potential level was significantly reduced,the MDA content was increased,and the GPX4 protein expression was down regulated.Therefore,the above study found that sodium selenite induced excessive accumulation of ROS in lung cancer A549 cells,caused massive depletion of intracellular GSH,leading to the decline of GPX4 expression,and inducing cell ferroptosis.
作者
时杰
王永安
孙基泽
石慧
盛洁
姚姚
嵇姗
SHI Jie;WANG Yongan;SUN Jize;SHI Hui;SHENG Jie;YAO Yao;JI Shan(Huishan District People′s Hospital,Wuxi City,Wuxi,Jiangsu 214000,China;Anhui Medical University,Hefei,Anhui 230000,China;Donghua University of Technology,Nanchang,Jiangxi 330000,China)
出处
《中国无机分析化学》
CAS
北大核心
2024年第1期124-130,共7页
Chinese Journal of Inorganic Analytical Chemistry
基金
安徽省高校自然科学研究项目(重点项目)(KJ2020A0196)
安徽省转化医学研究所研究基金资助项目(2022zhyx-C77)
安徽医科大学临床医学专业“早期接触科研”训练计划项目(2021-ZQKY-52)。