Department of General Surgery, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Oncol Rep. 2013 Nov;30(5):2153-60. doi: 10.3892/or.2013.2678. Epub 2013 Aug 20.
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.
肥胖增加胃癌的风险，并可能促进其生长，最近我们的新型体内小鼠模型证明了这一点。然而，这种相关性的潜在机制尚不清楚。本研究旨在探讨肥胖对胃癌生长的确切影响，并阐明潜在的分子机制。饮食诱导肥胖小鼠表现出胰岛素抵抗、葡萄糖不耐受和高血清内脂素浓度。在皮下小鼠模型中，与瘦小鼠相比，饮食诱导肥胖小鼠的肿瘤更具侵袭性。肿瘤重量与小鼠体重、血清胰岛素和内脂素浓度呈显著正相关。免疫组织化学染色显示，与瘦动物相比，肥胖小鼠皮下肿瘤中 iNampt、Sirt1 和 c-MYC 蛋白的表达水平上调。此外，肥胖不仅通过内分泌机制促使显著促进了小鼠胃前癌细胞的迁移、增殖，还影响了细胞凋亡和细胞周期。这与通过 RT-PCR 和 Western blot 证实的生存 nampt/sirt1/c-myc 正反馈环的表达增加有关。这些结果表明，饮食诱导的肥胖可能通过上调 nampt、sirt1 和 c-myc 基因的表达来促进小鼠胃癌的生长。
