胃癌是严重危害人类健康的恶性肿瘤。环境中的N-亚硝基化合物（NOCs）是胃癌发生发展重要诱因，然而其作用机制尚未阐明。研究报道N-甲基-N-硝基-N-亚硝基胍（MNNG，NOCs的一种）能诱导大鼠胃癌组织血管生成，我们也发现MNNG刺激胃癌细胞后，其条件上清明显促进血管内皮细胞管状形成，提示MNNG能诱导血管生成从而促进胃癌进展。生长抑制因子4（ING4）是抑制肿瘤血管生成重要分子，我们发现MNNG能抑制胃癌细胞ING4表达，而过表达ING4能显著抑制MNNG诱导胃癌血管生成，提示ING4是MNNG诱导胃癌血管生成重要分子。.研究包括：（1）细胞及动物模型验证ING4抑制MNNG诱导胃癌血管生成；（2）阐明ING4抑制MNNG诱导胃癌血管生成的分子机制，检测VEGF、MMP-2、MMP-9及其共同上游NF-κB信号通路变化。本研究将为针对NOCs的胃癌干预、预防和减缓胃癌进展提供理论依据。

Gastric cancer is the malignancy which endangers human health severely. N-nitroso compounds (NOCs) which exist in the environment are important causes for the tumorigenesis and progression of gastric cancer, but the mechanism isn’t fully elaborate. A study has reported that methylnitronitrosoguanidine (MNNG, one of NOCs) induced obvious angiogenesis in rat gastric cancer tissues, and in our study, we found that the conditional supernatant which was collected from the gastric cancer cells stimulated by MNNG promoted the vascular endothelial cell tube formation, these results suggested that MNNG could accelerate gastric cancer progression through inducing gastric cancer angiogenesis. Inhibitor of growth protein 4 (ING4) is an important molecule in inhibiting tumor angiogenesis, we found that MNNG could dramatically reduce the expression of ING4, and over-expression ING4 significantly inhibited the gastric cancer angiogenesis which was induced by MNNG, these results indicated that ING4 was a key molecule in gastric cancer angiogenesis induced by MNNG. .This study includes: (1) The cell and animal models will be used to validate that ING4 can inhibit gastric cancer angiogenesis induced by MNNG; (2) The exact mechanism of ING4 inhibiting gastric cancer angiogenesis induced by MNNG will be illustrated, and the changes of VEGF, MMP-2, and MMP-9 expression and their same upstream, NF-κB signal will be tested. The further study will provide theoretical basis for making interventions against NOCs for gastric cancer, preventing and slowing down the progression of gastric cancer.