Tivozanib reverses multidrug resistance mediated by ABCB1 (P-glycoprotein) and ABCG2 (BCRP).
Future Oncol
; 10(11): 1827-41, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24295377
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. MATERIALS &METHODS:
ABCB1- and ABCG2-overexpressing cell lines were treated with respective substrate antineoplastic agents in the presence or absence of tivozanib.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.CONCLUSION:
We conclude that tivozanib at noncytotoxic concentrations has the previously unknown activity of reversing multidrug resistance mediated by ABCB1 and ABCG2 transporters.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos de Fenilureia
/
Quinolinas
/
Transportadores de Cassetes de Ligação de ATP
/
Resistencia a Medicamentos Antineoplásicos
/
Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Revista:
Future Oncol
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China