| Background and Objective: Gastric carcinoma harms people's health fatally, whose pathogenesis, prevention and treatments are our research emphases. Cyclooxygenase is a rate-limiting enzyme involved in the conversion of arachidonic acid to prostaglandins. While COX-1 is constitutively expressed in a variety of tissue, COX-2 is a response gene induced by cytokines, growth factors, carcinogens, mitogens, onco-proteins, etc, overexpression of COX-2 was reported in various types of tumors and some precancerous tissues. Many epidemiological studies indicated that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) over one year could reduce the risk of esophageal, gastric, colorectal cancers. The lack of cox-2 gene or using rofecoxib, a COX-2 selective inhibitor, could greatly reduce polyps in APCA716 knockout mice. Clinical studies suggested that low-dose aspirin had a moderate chemo-preventive effect on adenomas in the large bowel. Sulindac and Celecoxib caused regression of colorectal adenomas of patients with familial adenomatous polyposis (FAP). The finding of NSAIDs' chemopreventive and chemotherapeutic effect brought great progress for preventions and treatments of cancers, especially digestive cancers. Unfortunately, the mechanisms ofCOX-2 expression have not been defined.Aberrant DNA methylation exists in carcinoma universally, manifested by wide DNAhypomethylation and local CpG island hypermethylation (mainly in promoter region). CpG island demethylation facilitates gene transcription, resulting in oncogene activation, chromosome instability, mutation hotspot, and retrotransposon replacement. CpG islandhypermethylation in promoter is one of the predominant mechanisms of inactivating various tumor suppressor genes in tumorigenesis. thereby aberrant DNA methylation is regarded as 'the third tumourigenesis pathway' hi two thousands year, Toyota et al suggested that COX-2 expression was inhibited by the aberrant methylation of exon 1 coding region of cox-2 gene in a subset of colorectal tumor cell lines and tissues, COX-2 expression could be restored by demethylation using the DNA methyltransferase inhibitor 5-aza-deoxycytidine. Later, Song et al reported that a completely methylated CpG island on the promoter of cox-2 gene accompanied with lack of COX-2 expression were found in gastric cancer cell line SUN-601. Furthermore, Inducing COX-2 expression is a important way for Hp promoted gastric cancer, in gastric cancer cell lines that exhibited a methylated CpG island on the promoter of cox-2 gene had no response to Hp, but when 5-azacytidine treated cells were subsequently stimulated with Hp, there were a 5-10 fold enhancement of both protein expression and release of the COX-2 product, prostaglandin Ea.These in vitro researches suggested that COX-2 expression had relationship with the methylation status of 5' CpG island of cox-2 gene. Consequently, we sought to compare the methylation status of 5' CpG island on both upstream and downstream of transcriptional start site of cox-2 gene in gastric cancer tissues to determine the mechanisms for COX-2 expression, distinguish the molecular character of gastric cancer, provide theoretic basis for clinical prevention and treatment individually of gastric cancer.Material and Methods: Forty-four primary gastric cancers were obtained from patients who received gastric carcinectomy in the First Affiliated Hospital of Zhengzhou University and Luoyang Oriental Hospital. Twelve para-carcinoma histological normal mucosas were used as control. Firstly, all the samples were proved histologically Methylation status of 5' end CpG island around the transcriptional start site of cox-2 gene was studied by PCR amplification after Hpa It -. Hha I restrictive enzyme cut; Immunohistochemical evaluation of COX-2 expression was also performed. P value less than 0.05 indicated statistical significance.Results: 1) Hpa IK Hha I sites were all methylated in twelve normal gastric mucosa tissues, whereas demethylated in 77.27%(34/44), 84.09%(37/44) gastric cancer...
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