Modulating the function of ABCB1: in vitro and in vivo characterization of sitravatinib, a tyrosine kinase inhibitor.

ABSTRACT:

Background

Overexpression of ATP-binding cassette (ABC) transporter is a major contributor to multidrug resistance (MDR), in which cancer cells acquire resistance to a wide spectrum of chemotherapeutic drugs. In this work, we evaluated the sensitizing effect of sitravatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), on ATP-binding cassette subfamily B member 1 (ABCB1)- and ATP-binding cassette subfamily C member 10 (ABCC10)-mediated MDR.

Methods

MTT assay was conducted to examine cytotoxicity and evaluate the sensitizing effect of sitravatinib at non-toxic concentrations. Tritium-labeled paclitaxel transportation, Western blotting, immunofluorescence analysis, and ATPase assay were carried out to elucidate the mechanism of sitravatinib-induced chemosensitization. The

SUBMITTER: Yang Y 

PROVIDER: S-EPMC7365458 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature