%0 Journal Article
%T Erlotinib inhibits progression to dysplasia in a colitis-associated colon cancer model
%A Beatriz Pag¨¢n
%A Angel A Isidro
%A Myrella L Cruz
%A Yuan Ren
%J World Journal of Gastroenterology
%D 2011
%I Baishideng Publishing Group Co. Limited
%R 10.3748/wjg.v17.i44.4858
%X 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% ¡À 11.47% vs 90.00% ¡À 10.00% in proximal, P < 0.05; 15.00% ¡À 8.19% vs 50.00% ¡À 16.67% in mid, P < 0.05; and 20.00% ¡À 9.17% vs 70.00% ¡À 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.
%K Animal model
%K Epidermal growth factor receptor
%K Colitis
%K Dysplasia
%K Erlotinib
%U http://www.wjgnet.com/1007-9327/full/v17/i44/4858.htm