Dioscin induces ferroptosis to suppress the metastasis of gastric cancer through the SLC7A11/GPX4 axis

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. The metastasis of gastric cancer cells is related to the regulation of ferroptosis;Dioscin induced ferroptosis in gastric cancer cells;Dioscin regulated the ferroptosis pathway to inhibit metastasis of gastric cancer cells. The metastasis of gastric cancer cells is related to the regulation of ferroptosis; Dioscin induced ferroptosis in gastric cancer cells; Dioscin regulated the ferroptosis pathway to inhibit metastasis of gastric cancer cells.