| Background and Obsjective:Gastric cancer is the major cause of cancer-related death in China and the world. Dalian, China is a high-risk area for GC, but the factors leading to this situation are still under investigation. Therefore, it is of great chemopreventive interest to unravel the underlying molecular events and interactions involved in stepwise gastrocarcinogenesis using GC tissues obtained from long-term residents of the Dalian area.Cyclooxygenase-2 is the rate-limiting enzyme in prostaglandin biosynthesis from arachidonic acid. COX-2 has been linked to cancer formation because its overexpression is associated with dysfunctional apoptosis and enhanced proliferation, angiogenesis, and tumorigenesis. Therefore, COX-2-oriented cancer therapy was proposed, and COX-2 inhibitors such as the nonsteroidal anti-inflammatory drugs (NSAIDs) showed promising anticancer efficacy in gastric carcinoma.A body of evidence has demonstrated that COX-2 expression can be triggered or enhanced by other cancer-associated events such as H. pylori infection, TNF-α-mediated NF-κB activation, and Wnt signaling. Induction of COX-2 expression is the early oncogenic event in the transformation of gastric epithelial cells infected with H. pylori. H. pylori can induce expression of host inflammatory genes such as TNF-αthat in turn activates NF-κB, a transcription factor whose target genes include COX-2. NF-κB is often constitutively activated in transformed gastric tissues. Similarly, the Wnt/?-catenin/TCF signaling pathway is integrally associated with tumor development and progression by activating transcription of downstream genes such as COX-2. Recent results showed that the Wnt/?-catenin signaling pathway was activated in most gastric cancers and was associated with tumor formation and progression. Taken together, the data described above point to an oncogenic role for COX-2 in...
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