Quercetin improves the efficacy of sorafenib in triple negative breast cancer cells through the modulation of drug efflux transporters expressions

Objective: This study aimed to investigate whether quercetin is able to improve the efficacy of sorafenib in triple negative breast cancer cells and explore the possibility of drug efflux transporters modulation by quercetin. Methods: We exposed MDA-MB-231, a triple negative breast cancer cell line, to several groups: Sorafenib alone, quercetin alone, a combination of sorafenib-quercetin, and control. We determined cell viability over control weekly up to 4 w. At the end of the fourth week, mRNA expressions of drug efflux transporters (P-glycoprotein and breast cancer resistance protein [BCRP] and MRP2 [multidrug resistance-associated protein-2]) were examined. Results: Sorafenib alone was shown to maintain its efficacy for only two weeks, while quercetin alone was able to maintain its effect for four weeks. A combination of sorafenib-quercetin showed the best cytotoxicity effects compared with sorafenib or quercetin alone and was able to maintain its efficacy for four weeks. There were increased mRNA expressions of P-glycoprotein, BCRP, and MRP2 after four weeks of treatment with sorafenib, while treatment with quercetin decreased the drug efflux transporters expressions. A combination of sorafenib-quercetin decreased the mRNA expressions of both P-glycoprotein and BCRP, compared with sorafenib alone. Conclusion: We suggest that decreased expressions of both drug efflux transporters, P-glycoprotein and BCRP, mediated by quercetin ameliorate the efficacy of sorafenib in TNBC. Therefore, the addition of quercetin to sorafenib might be useful in the future in improving the therapeutic efficacy of sorafenib in triple negative breast cancer.