Abstract
Chemotherapy is an irreplaceable treatment for prostate cancer. However, the acquisition of chemoresistance is a common and critical problem that requires urgent solutions for the effective treatment of this disease. The aim of the present study was to determine whether the combination of quercetin with doxorubicin reversed the resistance of prostate cancer cells to doxorubicin-based therapy. A prostate cancer (PC)3 cell line (PC3/R) with acquired doxorubicin-resistance was established. A significant drug-resistance to doxorubicin and high activation of the phosphoinositide 3-kinase/protein kinase-B (PI3K/AKT) pathway in PC3/R cells, compared with normal PC3 cells, was demonstrated. Notably, combination treatment of doxorubicin with quercetin significantly promoted the doxorubicin-induced apoptosis in PC3/R cells through the mitochondrial/reaction oxygen species pathway. In PC3/R cells, a significant upregulation of tyrosine-protein kinase-met (c-met) was observed compared with nromal PC3 cells. However, the response to quercetin treatment in PC3/R cells inhibited c-met expression and the downstream PI3K/AKT pathway. In addition, induced expression of c-met rescued quercetin-promoted apoptosis in PC3/R cells treated with doxorubicin. The results of the present study indicated that quercetin is able to reverse prostate cancer cell doxorubicin resistance by downregulating the expression of c-met. It may represent a potential strategy for reversing the chemoresistance of prostate cancer.