Quercetin reversed MDR in breast cancer cells through down-regulating P-gp expression and eliminating cancer stem cells mediated by YB-1 nuclear translocation

Abstract

Overexpression of P-glycoprotein (P-gp) plays an important role in mediating multidrug resistance (MDR), resulting in chemotherapy failure of tumor patients and enhancement of cancer stem cell characteristics. By preparing doxorubicin (Dox) resistant human breast cancer MCF-7 cells, here, we wanted to evaluate the effects of quercetin (Que) on MDR reversal activity and investigate its possible mechanism. MCF-7 and MCF-7/dox cells were respectively treated by Dox, paclitaxel (Pac), or vincristine (Vcr) with or without Que intervention for 24 hr. Cell viability, cell apoptosis, cell cycle, intracellular drug accumulation, the expression of P-gp and Y-box binding protein 1 (YB-1), and breast cancer stem cells (BCSCs) were then assessed. The results showed that Que significantly enhanced the antitumor activities of Dox, Pac, and Vcr in breast cancer cells. In addition, combined treatment of Dox, Pac, or Vcr with Que significantly downregulated P-gp expression and eliminated BCSCs. Furthermore, combined treatment of Dox, Pac, or Vcr with Que significantly inhibited nuclear translocation of YB-1. Thus, we speculated that Que reversed MDR in breast cancer cells through downregulating P-gp expression and eliminating cancer stem cells mediated by YB-1 nuclear translocation.