Lu Doudou, Yuan Ling, Wang Zhaozhao, Xu Duojie, Meng Fandi, Jia Shumin, Li Yahong, Li Weiqiang, Nan Yi
School of Clinical Medicine, Ningxia Medical University, Yinchuan, China.
College of Pharmacy, Ningxia Medical University, Yinchuan, China.
Free Radic Res. 2025 May;59(5):426-441. doi: 10.1080/10715762.2025.2515202. Epub 2025 Jun 13.
The prognosis of gastric cancer (GC) remains poor due to metastases and resistance to chemotherapy. Ferroptosis is a novel cell death regulation mode characterized by iron dependence and lipid peroxidation. Dioscin, a compound extracted from the Paris polyphylla rhizomes roots, has been shown to have an inhibitory effect on cancers. However, whether it induces ferroptosis to participate in anti-cancer metastasis remains unclear. The ability of gastric cancer cells to invade and migrate was evaluated by wound healing and transwell assays. Malondialdehyde (MDA), glutathione (GSH) assay kit, and dichlorofluorescin diacetate (DCFH-DA) fluorescent probes were used to detect ferroptosis in gastric cancer cells. The expression levels of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot methods. The rescue assay was performed by adding Ferrostatin-1 (Fer-1) co-treatment to verify that Dioscin inhibited gastric cancer metastasis by participating in ferroptosis. Dioscin inhibited gastric cancer cells' wound healing, migration, and invasion process. In addition, Dioscin increased the level of reactive oxygen species (ROS) and MDA while decreasing GSH level, and induced ferroptosis of gastric cancer cells. Fer-1, an inhibitor of ferroptosis, could reverse the effect of Dioscin. In terms of mechanism, Dioscin induced ferroptosis through SLC7A11/GPX4 axis and was involved in the regulation of inhibiting metastasis of gastric cancer. These results suggested that Dioscin was involved in anti-cancer metastasis by inducing ferroptosis.
由于转移和对化疗的耐药性，胃癌（GC）的预后仍然很差。铁死亡是一种以铁依赖性和脂质过氧化为特征的新型细胞死亡调节模式。薯蓣皂苷元是从七叶一枝花根茎中提取的一种化合物，已被证明对癌症有抑制作用。然而，它是否通过诱导铁死亡参与抗癌转移仍不清楚。通过伤口愈合和Transwell实验评估胃癌细胞的侵袭和迁移能力。使用丙二醛（MDA）、谷胱甘肽（GSH）检测试剂盒和二氯荧光素二乙酸酯（DCFH-DA）荧光探针检测胃癌细胞中的铁死亡。通过定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测谷胱甘肽过氧化物酶4（GPX4）和溶质载体家族7成员11（SLC7A11）的表达水平。通过添加铁死亡抑制剂Ferrostatin-1（Fer-1）共同处理进行挽救实验，以验证薯蓣皂苷元通过参与铁死亡抑制胃癌转移。薯蓣皂苷元抑制胃癌细胞的伤口愈合、迁移和侵袭过程。此外，薯蓣皂苷元增加了活性氧（ROS）和MDA水平，同时降低了GSH水平，并诱导胃癌细胞发生铁死亡。铁死亡抑制剂Fer-1可以逆转薯蓣皂苷元的作用。在机制方面，薯蓣皂苷元通过SLC7A11/GPX4轴诱导铁死亡，并参与抑制胃癌转移的调控。这些结果表明，薯蓣皂苷元通过诱导铁死亡参与抗癌转移。
