RESUMO
Objectives: To investigate the effects of bergapten of Angelicae Dahuricae Radix on the transport of vincristine and its possible mechanism. Methods: The apparent permeability coefficient (Papp) for the transport of vincristine through the membrane of MDCK-MDR1 cells was used as an indicator of the effect of bergapten on vincristine transport. Molecular docking was employed to predict the binding force between bergapten and P-glycoprotein (P-gp). The effects of bergapten on P-gp function and P-gp ATPase activity were determined by rhodamine 123 (Rho123) accumulation and activity analysis, respectively. 1,6-Diphenyl-1,3,5-hexatriene (DPH) was used to study the effects of bergapten on membrane fluidity, and Western blotting and quantitative real-time PCR assays were performed to analyze the effect of bergapten on the protein and mRNA expression of P-gp, respectively. These experiments clarified the effects of bergapten on the transport of vincristine and allowed exploration of the possible mechanism underlying the effects of bergapten. Results: The results showed that bergapten could inhibit the transport of vincristine in MDCK-MDR1 cells, and the binding force between bergapten and P-gp was weaker. Bergapten could reduce the accumulation of Rh123 in MDCK-MDR1 cells, increase the membrane fluidity, and upregulate P-gp protein and mRNA expression but it had no effect on P-gp ATPase activity. Conclusions: Overall, we concluded that the possible mechanism through which bergapten inhibits vincristine transport was related to the bergapten-mediated upregulation of P-gp protein and mRNA expression, membrane fluidity or P-gp enzyme activity.