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

作者：Ben Xu, Wei-Jie Zhu, Yiji Peng, Sida Cheng · 发表于：Translational Cancer Research · 年份：2021 · DOI：10.21037/tcr-21-227 · 被引用次数：47 · 研究领域：Ferroptosis and cancer prognosis、Curcumin's Biomedical Applications、Cancer, Lipids, and Metabolism

Background: To explore the possible mechanism by which curcumin reverses the sunitinib resistance in clear cell renal cell carcinoma (ccRCC). Methods: A sunitinib-resistant ccRCC cell model was established. The MTT assay was used to determine the half maximal inhibitory concentration (IC 50 ) 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 ADAMTS18 gene and ferroptosis-related proteins ( NCOA4, FTH1 and p53 ) 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- ADAMTS18 , cell proliferation activity was assessed by the CCK-8 assay, and the protein expression levels of ADAMTS18, NCOA1, FTH1 and p53 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. Results: Curcumin plus sunitinib inhibited the proliferation of sunitinib-resistant ccRCC cells (P<0.05). Curcumin significantly decreased the concentration of iron ion...