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erlotinib inhibits progression to dysplasia in a colitis-associated colon cancer model

World Journal of Gastroenterology 2011年第44期17卷 4858-4866页

作者： Beatriz Pagán Angel A Isidro Myrella L Cruz Domenico Coppola Caroline B Appleyard Department of Physiology and Pharmacology Ponce School of Medicine Department of Anatomic Pathology H.Lee Moffitt Cancer Center and Research Institute

AIM:To investigate the role of epidermal growth factor receptor(EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor ***: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 *** induce colitis-associated dysplasia,rats then received TNBS(iv) twice a week for 10 *** 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 *** rats were euthanized,the colons were removed and analyzed for damage and expression of the EGFR downstream effectors Erk1/2 and ***:Ninety percent of the vehicle-treated animals had dysplasia in any region of the ***-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 erlotinib-treated animals also had reduced cell proliferation,reduced active Erk1/2,and reduced c-Myc in colon epithelium compared with the vehicle-treated *** vitro,erlotinib treatment was shown to markedly decrease c-Myc and pErk1/2 levels in rat epithelial *** of rat epithelial cells was stimulated by epidermal growth factor and inhibited by erlotinib(P erlotinib can decrease the development of colitis-associated dysplasia,suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis.

关键词： animal model epidermal growth factor receptor colitis dysplasia erlotinib

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