title: Diet-induced obesity promotes murine gastric cancer growth through a nampt/sirt1/c-myc positive feedback loop.
abstract: Obesity increases the risk of gastric cancer and may promote its growth, as was recently demonstrated by our novel in vivo mouse model. However, the underlying mechanisms of this correlation remain unclear. The purpose of this study was to investigate the precise effects of obesity on gastric cancer growth and to elucidate the potential molecular mechanisms. Diet-induced obese mice were insulin-resistant, glucose-intolerant and had high serum visfatin concentration. In the subcutaneous mouse model, tumors were more aggressive in diet-induced obese mice compared with lean mice. Tumor weights showed a significant positive correlation with mouse body weights, as well as serum insulin and visfatin concentrations. Immunohistochemical staining showed that the expression levels of iNampt, Sirt1 and c-MYC proteins were upregulated in the subcutaneous tumors from obese mice compared to those from lean animals. Furthermore, obesity not only prompted significantly murine forestomach carcinoma cell migration, proliferation, but also affected cellular apoptosis and cell cycle by endocrine mechanisms. These were associated with increased expression of the pro-survival nampt/sirt1/c-myc positive feedback loop confirmed by RT-PCR and western blotting. These results suggested that diet-induced obesity could promote murine gastric cancer growth by upregulating the expression of the nampt, sirt1 and c-myc genes.
authors: Department of General Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors: Hai-Jun
authors: HJ
authors: Li
authors: Xiang-Ming
authors: XM
authors: Che
authors: Wei
authors: W
authors: Zhao
authors: Shi-Cai
authors: SC
authors: He
authors: Zheng-Liang
authors: ZL
authors: Zhang
authors: Rui
authors: R
authors: Chen
authors: Lin
authors: L
authors: Fan
authors: Zong-Liang
authors: ZL
authors: Jia
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000178:diet therapy / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology*
chemical_list: D016207:Cytokines; D016271:Proto-Oncogene Proteins c-myc; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1