蛇莓提取物通过GPX4诱导铁死亡抑制肾癌细胞OS-RC-2增殖OA北大核心CSTPCD

Aim To investigate the effect of ethanol extract of Duchesnea Indica on the proliferation of renal cell carcinoma OS-RC-2 cells induced by ferroptosis and the related mechanism.Methods Cell prolifera-tion was detected by the CCK-8 assay.The levels of ROS,GSH,MDA and apoptosis rate were detected by ROS detection,GSH kit,MDA kit and apoptosis Kit,respectively.The components and targets of Duchesnea Indica were analyzed by network pharmacology.The binding ability of Duchesnea Indica components to GPX4,the core target of ferroptosis,was detected by molecular docking.The key proteins in the ferroptosis signaling pathway were detected by Western blot.Next,ferroptosis inhibitor Fer-1 and ROS inhibitor NAC were used to detect the changes in cell prolifera-tion and ferroptosis related proteins.The cell prolifera-tion and the protein level of GPX4 were detected by the administration of Dulcitol.Results Duchesnea Indica inhibited cell proliferation in a time-concentration de-pendent manner,upregulated the level of ROS and MDA while down regulated GSH Flow cytometry showed that Duchesnea Indica significantly promoted cell apoptosis,but not in a concentration-dependent manner.The results of network pharmacology and mo-lecular docking showed that dulcitol had a stable bind-ing with GPX4(-6.5 kJ·mol-1).Western blot re-sults showed that Duchesnea Indica significantly de-creased GPX4 and SLC7A11,while increased HO-1 and Transferrin protein levels.The results of the rescue experiment showed that the co-administration of Fer-1/NAC and Duchesnea Indica could significantly reverse the cell viability and the changes in the protein levels of GPX4,SLC7A11,HO-1 and Transferrin,when compared to treated with Duchesnea Indica alone in OS-RC-2.Dulcitol in the alcohol extract of Duchesnea Indica could inhibit the proliferation of OS-RC-2 cells and reduce their GPX4 protein expression level.Con-clusion In summary,Duchesnea Indica could reduce the expression of GPX4,which further promotes prolif-eration inhibition and ROS accumulation in renal canc-er cells,driving cell iron death.Moreover,Dulcitol may be a potential pharmacodynamic substance that di-rectly acts on GPX4.