Curcumin reverses the sunitinib resistance in clear cell renal cell carcinoma (ccRCC) through the induction of ferroptosis via the ADAMTS18 gene
| Autor: | Wei-Jie Zhu, Si-da Cheng, Ben Xu, Yi-Ji Peng |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Curcumin clear cell renal cell carcinoma (ccRCC) Sunitinib business.industry Ferroptosis ADAMTS18 urologic and male genital diseases medicine.disease female genital diseases and pregnancy complications ferroptosis Clear cell renal cell carcinoma chemistry.chemical_compound Oncology chemistry sunitinib resistance medicine Cancer research Original Article Radiology Nuclear Medicine and imaging business Gene medicine.drug |
| Zdroj: | Translational Cancer Research |
| ISSN: | 2219-6803 2218-676X |
| Popis: | 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 (IC50) 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 (P0.05). Ferroptosis inhibitors reversed the inhibitory effect of curcumin on sunitinib-resistant ccRCC cell lines. Conclusions Curcumin can reverse the sunitinib resistance in ccRCC, possibly by upregulating the expression of the ADAMTS18 gene to induce ferroptosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|