Estudo da expressão de PHD3, HIF1-α e SOD1 em modelo experimental de câncer colorretal tabagista e resposta a radioterapia

• Ano de defesa: 2016
• Autor(a) principal: Trivilin, Leonardo Oliveira
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Doutorado em Biotecnologia; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Biotecnologia
• Palavras-chave em Português: Carcinogenesis; Cancer; Tobacco; Biomarkers; Colorectal; Carcinogênese; Neoplasia; Tabaco; Biomarcadores; Cólon e reto; Biotecnologia; 61
• Link de acesso: http://repositorio.ufes.br/handle/10/7130

Smoking is a risk factor for colorectal cancer development and interferes on protein expression involved on tumoral progression, prognostic and therapeutic response. Thus, the objective was to study PHD3, HIF1-α and SOD-1 expression, as well as response to radiotherapy in experimental model for colorectal cancer exposed to cigarette smoke. It was used 53 young male rats Wistar, weighing on average 181,35g (±18,7g). Five animals were kept as negative control DMH-/tobacco- (G0).The induction of colorectal carcinogenesis with DMH during five weeks has been conducted on 48 animals, divided on experimental groups consisting of 12 animals each: DMH+ group (G1), DMH+/radiotherapy group (G2), DMH+/tobacco+ group (G3) and DMH+/tobacco+/radiotherapy group (G4). The exposure of G3 and G4 groups to cigarette smoke occurred in inhalation chamber equipped with smoke puff, and corresponded to 12 cigarettes/day divided into two exposure shifts of 60 minutes each, over 143 days. In the 21th experiment week, G2 and G4 animals underwent three radiotherapy sessions at a dose of 700 cGy each, totaling 2500 cGy. At 22 weeks, all animals were euthanized for removal of >0.1 cm injuries, processed histologically and stained with Hematoxylin-Eosin for diagnosis. It was selected samples classified as tubular adenocarcinoma (G1, G2, G3, G4) and normal mucosa for immunohistochemical technique for proteins PHD3, HIF1-a, SOD1 and cleaved caspase-3. The radiation response was obtained by apoptotic index of G2 and G4 groups. In G1 group were found dysplastic lesions, benign and malignant, moderate to severe inflammation and severe to moderate pleomorphism. In G3 were found dysplastic and malignant lesions, mild to moderate inflammation and mild to moderate pleomorphism. PHD3 protein suffered downregulation in G1, G3 and G4, more expressed in G2 (p=0.0011). HIF1-α protein was less expressed in G1 (p=0.0005) and increased its expression in this group after radiotherapy compared to others. SOD-1 was more expressed in G1, and after radiotherapy in G4 (p=0.005). The apoptotic index was significantly higher in G4 (p = 0.0289). Malignancies were predominant in exposed to cigarette smoke experimental model indicating its use in studies of smokers prognostic and survival, through use of molecular tools and, PHD3 downregulation, HIF-1alpha upregulation and levels of SOD-1 lower than unexposed animals, led to better radiotherapy response.