课题组前期研究显示，COX-2在胃癌中高表达，能够通过NOTCH通路促进胃癌侵袭迁移，且可能与PI3K/Akt信号通路有关。但COX-2与NOTCH、Akt之间的作用机制尚不清楚。本研究通过在胃癌细胞中上调或下调COX-2、Akt的表达，研究Akt与NOTCH的相互作用，深入分析Akt与NOTCH的作用位点、Akt对NOTCH胞内段向核内移位以及对胃癌侵袭迁移的影响，阐明Akt与NOTCH之间相互作用的分子机制；进一步研究COX-2促进Akt磷酸化的作用位点及其对Akt磷酸化相关分子表达量的影响，证实COX-2促进Akt磷酸化的具体分子机制；通过体内外验证COX-2不同表达水平对胃癌侵袭迁移的影响，并检测侵袭相关分子的表达量变化，阐明COX-2影响胃癌侵袭迁移的效应分子。本课题组拟通过阐明COX-2通过PI3K/Akt通路作用于NOTCH的具体分子机制，为胃癌的诊断和治疗提供新的理论。

Previous studies have shown that COX-2 is highly expressed in gastric cancer, which can promote the invasion and migration of gastric cancer cells, cause the activation of NOTCH which may be related to the PI3K/Akt signaling pathway. However, the mechanism of between COX-2 and NOTCH and Akt is still unclear. In this study, the expression of COX-2 and Akt was up-regulated or down-regulated in gastric cancer cells, and the interaction between Akt and NOTCH was studied. The action sites of Akt and NOTCH, the effect of Akt on the transportation of NOTCH intracellular and the invasion and migration of gastric cancer were further analyzed, so as to clarify the molecular mechanism of the interaction between Akt and NOTCH. The specific molecular mechanism of COX-2 promoting Akt phosphorylation was confirmed by studying the action sites of COX-2 promoting Akt phosphorylation and its influence on the expression of Akt phosphorylation-related molecules. The effects of different COX-2 expression levels on the invasion and migration of gastric cancer were verified in vivo and in vitro, and the changes in the expression levels of invasion-related molecules were detected to clarify the effector molecules of COX-2 affecting the invasion and migration of gastric cancer. Our research intends to provide new theoretical evidence for the diagnosis and treatment of gastric cancer by clarifying the specific molecular mechanism of COX-2 acting on NOTCH through the PI3K/Akt pathway.