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Type: Artigo
Title: Obesity-induced increase in tumor necrosis factor-alpha leads to development of colon cancer in mice
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Author: Flores, M.B.S.
Rocha, G.Z.
Souza, D.M.D.
Costa, F.O.
Dias, M.M.
Ropelle, E.R.
Camargo, J.A.
Carvalho, R.B.
Carvalho, H.F.
Saad, M.J.A.
Carvalheira, J.B.C.
Abstract: Epidemiology studies have shown that obesity increases risk for colorectal cancer (CRC). We investigated the contribution of obesity-induced increases in levels of tumor necrosis factor (TNF)-alpha and hyperinsulinemia to the development of CRC in mice. METHODS: Lean and obese mice (C57BL6/J and ob/ob) were given a combination of azoxymethane and dextran sulfate sodium, which led to the development of CRC; lean and obese severe combined immunodeficient mice were injected with HT-29 cells. We analyzed the roles of TNF-alpha and insulin in the development of obesity-mediated CRC using immunoblot, immunohistochemical, and apoptosis assays. RESULTS: Genetic-and diet-induced obesity increased the incidence and size of tumors that developed after administration of azoxymethane and dextran sulfate sodium, compared with lean mice. HT-29 xenograft tumors grew more rapidly in obese than lean mice. Neutralization of TNF-alpha reduced activation of c-Jun N-terminal kinase, I kappa B kinase, and the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin signaling pathway; it also reduced the growth and development of tumors in obese mice. Reducing levels of insulin levels had no effect on tumor growth in obese mice. CONCLUSIONS: TNF-alpha contributes to colon tumor growth in obese mice. Reagents that inhibit TNF-alpha might prevent the development or progression of CRC in obese individuals
Subject: Inflamação
Resistência à insulina
Country: Estados Unidos
Editor: Elsevier
Citation: Gastroenterology. W B Saunders Co-elsevier Inc, v. 143, n. 3, n. 741, n. +, 2012.
Rights: fechado
Identifier DOI: 10.1053/j.gastro.2012.05.045
Date Issue: 2012
Appears in Collections:FCM - Artigos e Outros Documentos

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