Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance

Frontiers in Pharmacology

Qiu-Xu Teng¹  Jing-Quan Wang¹  Zi-Ning Lei¹  Dong-Hua Yang¹  Zhe-Sheng Chen¹  Jiang-Jiang Qin²  Jin-Yun Dong²  Zuodong Qin³  Wubliker Dessie³  Meifeng Wang³  Xiaofang Luo³ 

[1] Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY, United States;Institute of Cancer and Basic Medicine, Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China;Research Center of Biochemical Engineering Technology, College of Chemistry and Bioengineering, Hunan University of Science and Engineering, Yongzhou, China;

关键词: multidrug resistance;    ABC transporter;    antimicrobial peptide HX-12C;    reversal agents;    combination therapy;   

DOI  :  10.3389/fphar.2020.01208

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown