二氢青蒿素（dihydroartemisinin,DHA）是青蒿素的一种衍生物，在多种肿瘤中表现出明显的抗肿瘤活性，但其具体机制不详。本文探讨了DHA对肝癌细胞的毒性作用机制。利用CCK-8试剂检测DHA对肝癌细胞株活力的影响，通过荧光探针染色及流式细胞术分析细胞内ROS及脂质过氧化物水平的变化；通过谷胱甘肽测定试剂盒检测细胞内还原型谷胱甘肽含量的变化，并通过免疫印迹分析DHA作用下细胞内铁死亡通路蛋白质中GPX4的变化。结果发现，DHA能显著抑制SMMC-7721及Huh-7细胞活力，其半数抑制浓度分别为23.74 μmol/L及26.92 μmol/L。 在35 μmol/L DHA 处理下，SMMC-7721及Huh-7细胞内ROS分别升高2.6倍和2.1倍，脂质过氧化物升高2.3倍和1.7倍。DHA可诱导细胞内GSH含量下降，并能下调铁死亡相关蛋白质GPX4蛋白水平。通过利用小分子抑制剂进行功能恢复实验发现，ROS抑制剂、铁螯合剂及铁死亡抑制剂都可不同程度恢复DHA引起的细胞活力下降。进一步检测发现，铁死亡抑制剂可抑制DHA诱导的脂质过氧化，并恢复GSH含量及GPX4蛋白水平。结果表明，在肝癌细胞中，DHA可通过诱导细胞发生铁死亡抑制肝癌细胞生长
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