Cetuximab enhanced the efficacy of chemotherapeutic agent in ABCB1/P-glycoprotein-overexpressing cancer cells

摘要: The overexpression of ATP-binding cassette (ABC) transporters is closely associated with the development multidrug resistance (MDR) in certain types cancer, which represents a formidable obstacle to successful cancer chemotherapy. Here, we investigated that cetuximab, an EGFR monoclonal antibody, reversed chemoresistance mediated by ABCB1, ABCG2 or ABCC1. Our results showed cetuximab significantly enhanced cytotoxicity ABCB1 substrate agent ABCB1-overexpressing MDR cells but had no effect their parental drug sensitive and ABCC1, overexpressing cells. Furthermore, markedly increased intracellular accumulation doxorubicin (DOX) rhodamine 123 (Rho 123) concentration-dependent manner. Cetuximab stimulated ATPase activity did not alter expression level block phosphorylation AKT ERK. Interestingly, decreased cell membrane fluidity was known decrease function ABCB1. findings advocate further clinical investigation combination chemotherapy conventional chemotherapeutic drugs patients.