Modulation of signaling enhances the efficacy of the combination of satraplatin and erlotinib.
Curr Drug Targets
; 15(14): 1312-21, 2014.
Article
em En
| MEDLINE
| ID: mdl-25382189
ABSTRACT
UNLABELLED The active metabolite (JM118) of the oral platinum analog satraplatin (JM216) was investigated for potential synergism with erlotinib, an epidermal growth factor receptor (EGFR) inhibitor. JM118 sensitivity of 7 cancer cell lines (ovarian 2008, A2780; colon Lovo92, WiDr; lung A549, SW1573; epidermoid A431), was enhanced most pronounced when JM118 preceded erlotinib, which was associated with increased formation of DNA-platinum adducts. The combination increased G2/M phase accumulation and enhanced apoptosis. JM118 increased the phosphorylation of the cell cycle proteins CDK2 and CHK1 after 24 hr exposure. JM118/erlotinib enhanced Erk and Akt phosphorylation after 2 hr. JM118 significantly decreased the phosphorylation of PTEN, VEGFR, EPHA1, ERBB4, FGF-R, andSTAT3 by 20 (PTEN) to >90% (STAT3). CONCLUSION:
Erlotinib enhanced the effects of JM118, even in cells with mutations in Ras. The mechanism of synergy involved a combination of effects on platinum-DNA adduct formation, cell cycle distribution and signaling.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Compostos Organoplatínicos
/
Quinazolinas
/
Transdução de Sinais
/
Adutos de DNA
/
Neoplasias
/
Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article