Influência da exposição à fumaça do cigarro e radioterapia na expressão de PHD3, HIF-1α, VEGF, SOD-1, RA2A e Foxp3 em células do infiltrado inflamatório de câncer colorretal induzido

• Ano de defesa: 2018
• Autor(a) principal: Mendes, Suzanny 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: Colorectal cancer; Gene expression; Tumor progression; Oxidative stress; Imunossupression; Câncer colorretal; Expressão gênica; Progressão tumoral; Estresse oxidativo; Imunossupressão; Biotecnologia; 61
• Link de acesso: http://repositorio.ufes.br/handle/10/10083

Smoking is the most leading cause of preventable death in the world, and is linked to the emergence of various types of tumors, including colorectal cancer. Studies with solid tumors show hypoxia as an important prognostic predictor and hypoxia and oxidative stress pathways, as well as immunosuppresion, may influence tumor progression, treatment and immune response. Since these pathways may have its genes expression altered by smoke and radiotherapy exposure, the present study sought to investigate explosion influence on PHD3, HIF-1α, VEGF, RA2A e Foxp3 protein expression in intra and peritumoral infiltrates of induced colorectal cancer. For this, 53 Wistar rats were used, 5 as negative control (G0) and the remaining 48 were induced to colorectal tumorigenesis with 1,2-dimethylhydrazine (DMH) and divided into 4 groups, DMH Group (G1), DMH/Radiotherapy Group (G2), DMH/Smoke Group (G3) and DMH/Smoke/Radiotherapy Group (G4). Exposure to cigarette smoke from G3 and G4 groups occurred in a inhalation chamber and corresponded to 12 cigarettes per day/group for 20 weeks. On 21st week, the animals of group G2 and G4 were submitted to three sessions of radiotherapy at the dose of 700 cGy each, totaling 2500 cGy. At 22nd week, animals were euthanized and the entire large intestine was open for removal of lesions, which were fixed and processed for inclusion in paraffin, and stained with hematoxylin and eosin for diagnosis. Lesions classified as Tubular Adenocarcinoma were submitted to immunohistochemistry for PHD3, HIF-1α, VEGF, hypoxia pathway, SOD-1 oxidative stress pathway and RA2A and Foxp3 immunosuppressive pathways. All tumor samples and controls were analyzed in intra- and peritumoral infiltrates semi-quantitatively and evaluated for exposure to cigarette smoke and radiotherapy in modulating the expression of these proteins. The response to radiotherapy was also evaluated by apoptotic index through caspase-3 cleaved antibody in samples belonging to groups G2 and G4. The results showed a relationship between exposure to cigarette smoke and radiotherapy with altered expression of proteins in intra- and peritumoral inflammatory infiltrates. Protein expression may differ between inflammatory infiltrates, and differ from expression in tumor cells, it shows the importance of differential function of these cells in the tumor microenvironment. In addition, the group exposed to smoke and radiotherapy presented better histopathological characteristics in relation to malignancy and better therapeutic response. Thus, we concluded that mice exposed to cigarette smoke and treated with radiotherapy presented better histochemical parameters of markers of cell death, inflammation, tumor progression, oxidative stress and response to radiotherapy than those not exposed to cigarette smoke. Since smoke is consecrated as a tumor inducer in several stages of tumorigenesis, and our results showed opposite characteristics, we suggest the need for new studies that confirm the real impact of smoking in the processes of tumorigenesis.