[Transmembrane transport activity of paclitaxel regulated by fangchinoline in MDR1-mDCK II cells].

Abstract

OBJECTIVE: To research the regulation of transmembrane transport activity of paclitaxel influenced by fangchinoline in MDR1-MDCK II cells. METHOD: Paclitaxel, one of the substrate of P-gp, was selected as the model drug. Verapamil hydrochloride was adopted as the active control to investigate the bilateral transport activity of paclitaxel regulated by fangchinoline in MDR1-MDCK II cells. RP-HPLC was applied to determine the concentration of paclitaxel in the transporting medium, which was used to calculate apparent permeability coefficient of paclitaxel across MDR1-MDCK I1 monolayer cells. RESULT: The efflux rate of paclitaxel was faster than the absorption rates across the MDR1-MDCK II monolayer cells with highly expressed P-gp. The absorption rates of paclitaxel combinated with fangchinoline and verapamil hydrochloride respectively were remarkably increased and the efflux rate was decreased. The reversal effect of the fangchinoline was stronger than the verapamil hydrochloride with the same molar concention. CONCLUSION: Fangchinoline can apparently decrease the efflux of paclitaxel and inhibit the multidrug resistance of antitumor drug mediated by P-gp.