Abstract:
OBJECTIVE To investigate the role and mechanisms of quercetin in reversing the cisplatin-resistance in the bladder cancer cells.
METHODS MTT assay was performed to measure the viability of cisplatin-resistant T24 bladder cancer cells treated with quercetin and cisplatin. Flow cytometry analysis was performed to measure the apoptosis of cisplatin-resistant T24 bladder cancer cells treated with quercetin and cisplatin. Western blot analysis was performed to evaluate the expression of Bim, cleaved caspase-9, cleaved caspase-3, and release of cytochrome C and Smac/DIABLO in the cisplatin-resistant T24 bladder cancer cells treated with quercetin and cisplatin. Co-immunoprecipitation analysis was performed to evaluate the interaction of Bim with Bak and Bax in the cisplatin-resistant T24 bladder cancer cells treated with quercetin and cisplatin.
RESULTS The sensitivity of cisplatin-resistant T24 cells to cisplatin was significantly lower than the routine T24 cells. The results of MTT assay and flow cytometry analysis showed that combination with quercetin could significantly promote the cisplatin-induced cell death and apoptosis in the cisplatin-resistant T24 cells. The results of co-immunoprecipitation and western blot analysis showed that quercetin significantly up-regulated the expression of Bim, which could interact with Bak and Bax, leading to the opening of mitochondrial membrane pore and the subsequent release of cytochrome C and Smac/DIABLO to the cytoplasm, and finally, the caspase-9 and caspase-3 was triggered.
CONCLUSION Quercetin rises the sensitivity of cisplatin-resistant bladder cancer cells to cisplatin through the Bim-Bak/Bax pathway.