Although its mechanisms remain unidentified, resveratrol (trans-3,4',5-trihydroxystilbene; RES), which is an active, low molecular-weight compound, possesses a unique antitumor function and is capable of enhancing the cytotoxicity of doxorubicin (DOX) within solid tumor cells. RES is hypothesized to exert these effects by reversing the multidrug resistance (MDR) of the cancer cells in response to chemotherapeutic agents. The aim of the present study was to investigate the reversal effect of RES on MDR in human breast cancer DOX-resistant (MCF-7/DOX) cells and investigate the underlying mechanisms of RES. The results demonstrated that RES inhibited the proliferation of MCF-7/DOX and MCF-7 cells in a dose-dependent manner. Moreover, RES enhanced the cytotoxicity of DOX on MCF-7/DOX cells and the reversal index of RES treatment was demonstrated to be significantly higher when compared with that of the group without RES treatment. In addition, RES was observed to reverse the MDR of the MCF-7/DOX cells and elevate the concentration of DOX in the MCF-7/DOX cells. Furthermore, RES was identified to significantly downregulate the MDR-1 gene and P-glycoprotein expression levels. Reversing MDR, via the downregulation of MDR-1 expression, was concluded to be a mechanism of RES, which enables the unique antitumor function of this polypeptide. Therefore, the present study indicated that RES may be a novel MDR reversal agent for the treatment of breast cancer.
Keywords: human breast cancer doxorubicin-resistant cell; multidrug resistance; resveratrol.