| 2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC) is a chalcone, which is isolated from the buds of Cleistocalyx operculatus. Multidrug resistance (MDR) refers to the tumor cells with anticancer drug resistance, while the various other anticancer drugs that are structurally and functionally different from the initial chemotherapy are also produce cross-resistance, is a major obstacle in the chemotherapeutic treatment of many human cancers. In this paper, we studied the reversal effect and mechanism of DMC on human hepatocellular carcinoma drug-resistant cells BEL-7402/5-FU in vitro and vivo.Administration of DMC reversed the multi-drug resistance of human hepatocellular carcinoma BEL-7402/5-FU cells significantly. DMC enhanced the sensitivity of BEL-7402/5-FU cells to 5-fluorouracil (5-FU) and Doxorubicin (DOX). Staining with Hoechst 33258 and Flow cytometric analysis showed that DMC had apoptosis-inducing effect on BEL-7402/5-FU cells. It could also increase the concentration of 5-FU in the resistant multi-drug-resistant cells. We also observed that over-expression of the multi-drug resistance-associated protein (MRP1) and GST-Ï€contributed to MDR in BEL-7402/5-FU cells. The mRNA and protein expression of MRP1 were decreased by DMC.Besides, we investigate the modulatory effect of DMC on the antitumor effect of 5-FU in resistant hepatic tumor xenograft. Resistant BEL-7402/5-FU cells were implanted subcutaneously in nude mice. Combined 5-FU and DMC (40mg/kg) treatment significantly elevated tumor inhibition rate to 72.2%. DMC could also increase 5-FU concentrations in tumor tissues and increase Caspase-3 activity. Besides, combined therapy resulted in enhanced tumor apoptotic and reduced proliferative activities relative to 5-FU alone. Examining body weight and adverse effects of the different treatment groups revealed no significant signs of toxicity. These findings suggest that DMC could effectively reverse reverses 5-FU resistance in vitro and vivo.
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