目的 探究白凤菜总黄酮通过调控核因子E2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）信号通路诱导铁死亡，从而抑制结肠癌HT29细胞生长。方法 采用CCK-8、流式细胞术检测白凤菜总黄酮对HT29细胞增殖、凋亡与周期的影响；通过铁代谢指标检测、RT-qPCR与Western blotting分析铁死亡相关基因与蛋白表达。结果 随着白凤菜总黄酮浓度的升高，HT29细胞的增殖抑制率逐渐增加，诱导细胞早期和晚期凋亡率显著升高，并引起细胞周期阻滞（P＜0.05、0.001）。白凤菜总黄酮可以显著提升细胞内活性氧（ROS）、亚铁离子、丙二醛（MDA）水平，降低谷胱甘肽（GSH）含量（P＜0.01、0.001）；上调HT29细胞中NFE2L2、HMOX1、ACSL4、TF、TFRC mRNA表达，下调谷胱甘肽过氧化物酶4（GPX4）mRNA表达（P＜0.05、0.01、0.001）。白凤菜总黄酮可上调铁死亡相关蛋白Nrf2、HO-1、TF的表达，下调GPX4蛋白表达（P＜0.05、0.001）。结论 白凤菜总黄酮可通过调控Nrf2/HO-1通路诱导铁死亡，从而抑制结肠癌HT29细胞增殖并促进凋亡。

Objective To investigate total flavonoids from Gynura formosana inhibit the growth of colon cancer HT29 cells by inducing ferroptosis through the regulation of the Nrf2/HO-1 signaling pathway.Methods Effects of total flavonoids from Gynura formosana on the proliferation, apoptosis, and cycle of HT29 cells were assessed using CCK-8 and flow cytometry. Detection of iron metabolism indicators, RT-qPCR, and Western blotting analysis were performed to evaluate the expression of genes and proteins associated with ferroptosis. Results As the total flavonoid concentration of Gynura formosana increased, the proliferation inhibition rate of HT29 cells gradually increased, and the rates of early and late apoptosis of the cells significantly increased, causing cell cycle arrest (P < 0.05, 0.001). The total flavonoids of Gynura formosana can significantly increase the levels of ROS, ferrous ions, and MDA in cells, while reducing the content of GSH (P < 0.01, 0.001), andup-regulate the mRNA expressions of NFE2L2, HMOX1, ACSL4, TF, and TFRC in HT29 cells, and down-regulate the mRNA expression of GPX4 (P < 0.05, 0.01, 0.001). The total flavonoids of Gynura formosana can up-regulate the expressions of iron death-related proteins Nrf2, HO-1, and TF, and down-regulate the protein expression of GPX4 (P < 0.05, 0.001). Conclusion Total flavonoids of Gynura formosana can inhibit the proliferation and promote the apoptosis of colon cancer HT29 cells by inducing ferroptosis through the regulation of the Nrf2/HO-1 pathway.

R285.5;R286.4

福建省中青年教师教育科研项目（科技类）（JAT251323）；漳州卫生职业学院院级科研项目（ZWYZ202411）