Curcumin reverses the sunitinib resistance in clear cell renal cell carcinoma (ccRCC) through the induction of ferroptosis via the ADAMTS18 gene

To explore the possible mechanism by which curcumin reverses the sunitinib resistance in clear cell renal cell carcinoma (ccRCC). A sunitinib-resistant ccRCC cell model was established. The MTT assay was used to determine the half maximal inhibitory concentration (IC ) and drug resistance (DR) index. The effects of curcumin plus sunitinib or sunitinib alone on drug-resistant cell lines were verified by the cell counting kit-8 (CCK-8)assay, colony formation assay, and apoptosis assay. The concentration of iron ions in the cell lines was analyzed using an Abcam Iron Assay Kit. The expressions of gene and ferroptosis-related proteins ( and ) after curcumin plus sunitinib treatment were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. After transfection of curcumin plus sunitinib/sunitinib alone-treated drug-resistant cell lines with si- , cell proliferation activity was assessed by the CCK-8 assay, and the protein expression levels of and were analyzed by Western blotting. After treatment with ferroptosis-1 (Fer-1; a ferroptosis inhibitor), the cell proliferation activity of drug-resistant cell lines treated with curcumin plus sunitinib/sunitinib alone was reassessed using the CCK-8 assay. Curcumin plus sunitinib inhibited the proliferation of sunitinib-resistant ccRCC cells (P