Erlotinib inhibits progression to dysplasia in a colitis-associated colon cancer model.
World J Gastroenterol
; 17(44): 4858-66, 2011 Nov 28.
Article
en En
| MEDLINE
| ID: mdl-22171126
ABSTRACT
AIM:
To investigate the role of epidermal growth factor receptor (EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor erlotinib.METHODS:
Sprague-Dawley rats received trinitrobenzene sulfonic acid (TNBS; 30 mg in 50% ethanol, ic), followed 6 wk later by reactivation with TNBS (5 mg/kg, iv) for 3 d. To induce colitis-associated dysplasia, rats then received TNBS (iv) twice a week for 10 wk. One group received erlotinib (10 mg/kg, ip) for 1 wk before the start of the reactivation of the colitis and 2 wk after (21 d); the rest received the vehicle. After rats were euthanized, the colons were removed and analyzed for damage and expression of the EGFR downstream effectors Erk1/2 and c-Myc.RESULTS:
Ninety percent of the vehicle-treated animals had dysplasia in any region of the colon. Erlotinib-treated animals had a significant decrease in the incidence of dysplasia compared to vehicle-treated animals in all regions of the colon (50.00% ± 11.47% vs 90.00% ± 10.00% in proximal, P < 0.05; 15.00% ± 8.19% vs 50.00% ± 16.67% in mid, P < 0.05; and 20.00% ± 9.17% vs 70.00% ± 15.28% in distal, P < 0.01). Erlotinib-treated animals also had reduced cell proliferation, reduced active Erk1/2, and reduced c-Myc in colon epithelium compared with the vehicle-treated animals. In vitro, erlotinib treatment was shown to markedly decrease c-Myc and pErk1/2 levels in rat epithelial cells. Proliferation of rat epithelial cells was stimulated by epidermal growth factor and inhibited by erlotinib (P < 0.05).CONCLUSION:
Erlotinib can decrease the development of colitis-associated dysplasia, suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Quinazolinas
/
Colitis
/
Neoplasias del Colon
/
Progresión de la Enfermedad
/
Inhibidores de Proteínas Quinasas
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
World J Gastroenterol
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos