Produção Nacional
Revisado por pares
RETRACTED: Obesity-Induced Increase in Tumor Necrosis Factor-α Leads to Development of Colon Cancer in Mice
2012; Elsevier BV; Volume: 143; Issue: 3 Linguagem: Inglês
10.1053/j.gastro.2012.05.045
ISSN1528-0012
AutoresMarcelo B.S. Flores, Guilherme Z. Rocha, Danilo Marchete Damas-Souza, Felipe Osório–Costa, Marília M. Dias, Eduardo R. Ropelle, Juliana Alves de Camargo, Rita Barbosa de Carvalho, Hernandes F. Carvalho, Mário J.A. Saad, José Barreto Campello Carvalheira,
Tópico(s)Cancer-related Molecular Pathways
ResumoBACKGROUND & AIMS: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)-␣ 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-␣ 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-␣ reduced activation of c-Jun N-terminal kinase, IB 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-␣ contributes to colon tumor growth in obese mice.Reagents that inhibit TNF-␣ might prevent the development or progression of CRC in obese individuals.
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