Multidrug resistance (MDR) of
tumor cells to chemotherapeutic agents is the main reason for the failure of
cancer chemotherapy. Overexpression of ABCB1 transporter that actively pumps various drugs out of the cells has been considered a major contributing factor for MDR. Over the past decade, many
antimicrobial peptides with antitumor activity have been identified or synthesized, and some antitumor
peptides have entered the clinical practice. In this study, we report that
peptide HX-12C has the effect of reversing ABCB1-mediated
chemotherapy resistance. In ABCB1-overexpressing cells, nontoxic dose of
peptide HX-12C inhibited drug resistance and increased the effective intracellular concentration of
paclitaxel and other ABCB1 substrate drugs. The mechanism study showed that
peptide HX-12C stimulated ABCB1
ATPase activity without changing the expression level and localization patterns of ABCB1. Molecular docking predicted the binding modes between
peptide HX-12C and ABCB1. Overall, we found that
peptide HX-12C reverses ABCB1-mediated MDR through interacting with ABCB1 and blocking its function without affecting the transporter's expression and cellular localization. Our findings suggest that this
antimicrobial peptide may be used as a novel prospective
cancer therapeutic strategy in combination with conventional
anticancer agents.