Masitinib Antagonizes ATP-binding Cassette Subfamily G Member 2-mediated Multidrug Resistance

Overview

Journal Int J Oncol

Specialty Oncology

Date 2014 Mar 15

PMID 24626598

Citations 15

Authors

Rishil J Kathawala

Jun-Jiang Chen

Yun-Kai Zhang

Yi-Jun Wang

Atish Patel

De-Shen Wang

Tanaji T Talele

Charles R Ashby Jr

Zhe-Sheng Chen

Affiliations

Soon will be listed here.

Abstract

In this in vitro study, we determined whether masitinib could reverse multidrug resistance (MDR) in cells overexpressing the ATP binding cassette subfamily G member 2 (ABCG2) transporter. Masitinib (1.25 and 2.5 µM) significantly decreases the resistance to mitoxantrone (MX), SN38 and doxorubicin in HEK293 and H460 cells overexpressing the ABCG2 transporter. In addition, masitinib (2.5 µM) significantly increased the intracellular accumulation of [(3)H]-MX, a substrate for ABCG2, by inhibiting the function of ABCG2 and significantly decreased the efflux of [(3)H]-MX. However, masitinib (2.5 µM) did not significantly alter the expression of the ABCG2 protein. In addition, a docking model suggested that masitinib binds within the transmembrane region of a homology-modeled human ABCG2 transporter. Overall, our in vitro findings suggest that masitinib reverses MDR to various anti-neoplastic drugs in HEK293 and H460 cells overexpressing ABCG2 by inhibiting their transport activity as opposed to altering their levels of expression.

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