In vitro and in vivo identification of ABCB1 as an efflux transporter of bosutinib.

ABSTRACT:

Background

Bosutinib is a recently approved ABL inhibitor. In spite of the well-documented effectiveness of BCR-ABL inhibitors in treating chronic myeloid leukemia, development of resistance is a continuous clinical challenge. Transporters that facilitate drug uptake and efflux have been proposed as one potential source of resistance to tyrosine kinase inhibitor treatment. Our aim was to determine which carriers are responsible for bosutinib transport.

Methods

K562S cells overexpressing the drug transporters ABCB1, ABCG2, and SLC22A1 were generated, characterized and used in proliferation assay and intracellular uptake and retention assay (IUR). In vivo experiments were performed in nude mice injected with K562S, K562DOX cells (overexpressing ABCB1), and K562DOX silenced for

SUBMITTER: Redaelli S 

PROVIDER: S-EPMC4491863 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature