Reduce Doxorubicin Resistant by Inhibiting ABC Efflux Transporters Proteins

Abstract Background: Many aspects of medication absorption are impacted by ATP-binding cassette efflux transporters (ABC). These efflux protein restrict the availability of many different chemicals, including those used to treat cancer. Doxorubicin is one of the common anticancer drugs that suffering from resistant and low cell penetration. Methods: In this study, assessing the permeability of two BCRP substrates, pantoprazole and doxorubicin, in the rat everted gut, the effects of resveratrol and vinblastine on BCRP efflux activity were determined. In addition, Caco-2 cells were utilized to investigate the impact of BCRP inhibition on doxorubicin uptake by cells. The concentrations of pantoprazole and doxorubicin that absorbed through the intestinal membrane of everted gut were measured by HPLC with or without resveratrol and vinblastine at several time interval (10, 20, 30, 40 and 60 min) by using in vitro everted gut. Results: Incubation for 60 min showed the penetration of pantoprazole with resveratrol and vinblastine was significantly increased by 1.6 and 1.5- fold. Furthermore, doxorubicin that penetrates over the intestine membrane raised significantly (p ≤0.001) while it was treated with pantoprazole, by 1.8. Where are resveratrol and vinblastine increase doxorubicin absorbency by 1.6 and 1.5 fold, respectively. Caco-2 cells uptake of doxorubicin was raised when pantoprazole was present, resveratrol and vinblastine by 1.9 fold, 1.65 fold and 1.5 fold, correspondingly. Conclusion: This current study is a novel research which showed the inhibitory impact of resveratrol and vinblastine on BCRP-protein efflux activity in GIT tract and thus increases the doxorubicin bioavailability.