Effects of quercetin on p-gp and COX-2 expression and anticancer activity of paclitaxel in multidrug resistance cancer cell lines

摘要

Multidrug resistance (MDR) is a major cause of failures in cancer chemotherapy. Among several mechanisms of MDR, drug efflux by p-gp has been known as the most clinically significant one. There have been extensive efforts to overcome MDR by using drug delivery systems and p-gp inhibitors. Unfortunately, many of chemically synthesized p-gp inhibitors were not satisfactory due to their toxicity. In recent years, many researchers have turned their focuses on naturally occurring compounds as candidates of p-gp inhibitors. In the present study, quercetin, a naturally occurring flavonoid, was chosen as p-gp inhibitor to overcome MDR and enhance anticancer activity of anticancer agents such as paclitaxel which are p-gp substrates. Quercetin inhibited expression of p-gp in p-gp over-expressing cancer cell lines; MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7 and caco-2 which is a colorectal adenocarcinoma cell lines. In addition, quercetin also decreased the expression of cyclooxygenase-2 (COX-2) which has been known to have a positive correlation with p-gp expression in MDR cells. Quercetin was not cytotoxic at lower concentration in MCF-7/ADR and caco-2 although higher concentration of quercetin showed cell killing activity. The combination of low dose quercetin with paclitaxel enhanced anticancer activity of paclitaxel in MCF-7/ADR and caco-2. Taken together, quercetin showed potential as adjuvant in chemotherapy for the treatment of MDR cancer.