Back to Search
Start Over
Tivozanib reverses multidrug resistance mediated by ABCB1 (P-glycoprotein) and ABCG2 (BCRP).
- Source :
-
Future oncology (London, England) [Future Oncol] 2014 Aug; Vol. 10 (11), pp. 1827-41. Date of Electronic Publication: 2013 Dec 03. - Publication Year :
- 2014
-
Abstract
- Aim: This study aimed to investigate the mechanism of reversal of multidrug resistance mediated by ABC transporters with tivozanib (AV-951 and KRN-951). Tivozanib is a potent inhibitor of VEGF-1, -2 and -3 receptors.<br />Materials & Methods: ABCB1- and ABCG2-overexpressing cell lines were treated with respective substrate antineoplastic agents in the presence or absence of tivozanib.<br />Results: The results indicate that tivozanib can significantly reverse ABCB1-mediated resistance to paclitaxel, vinblastine and colchicine, as well as ABCG2-mediated resistance to mitoxantrone, SN-38 and doxorubicin. Drug efflux assays showed that tivozanib increased the intracellular accumulation of substrates by inhibiting the ABCB1 and ABCG2 efflux activity. Furthermore, at a higher concentration, tivozanib inhibited the ATPase activity of both ABCB1 and ABCG2 and inhibited the photolabeling of ABCB1 or ABCG2.<br />Conclusion: We conclude that tivozanib at noncytotoxic concentrations has the previously unknown activity of reversing multidrug resistance mediated by ABCB1 and ABCG2 transporters.
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B genetics
ATP Binding Cassette Transporter, Subfamily B metabolism
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters metabolism
Adenosine Triphosphatases metabolism
Antineoplastic Agents pharmacology
Cell Line, Tumor
Dose-Response Relationship, Drug
Enzyme Activation drug effects
Gene Expression
Humans
Inhibitory Concentration 50
Neoplasm Proteins metabolism
Phenylurea Compounds toxicity
Quinolines toxicity
Receptors, Vascular Endothelial Growth Factor antagonists & inhibitors
ATP-Binding Cassette Transporters genetics
Drug Resistance, Neoplasm genetics
Neoplasm Proteins genetics
Phenylurea Compounds pharmacology
Quinolines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1744-8301
- Volume :
- 10
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Future oncology (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 24295377
- Full Text :
- https://doi.org/10.2217/fon.13.253