Effects Of Deficiency Of COX-1 or COX-2 On Chemically-In

COX-1 或 COX-2 缺乏对化学输入的影响

• 批准号: 6546704
• 负责人: Robert Langenbach
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6546704
• 关键词: adenocarcinoma; azo compounds; cancer prevention; chemical carcinogen; chemical carcinogenesis; chemoprevention; colon polyp; colorectal neoplasms; enzyme deficiency; enzyme inhibitors; gastrointestinal neoplasms; laboratory mouse; methane; nonsteroidal antiinflammatory agent; preneoplastic state; prostaglandin endoperoxide synthase; protein isoforms

Epidemiology data indicate that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the incidence of colorectal cancer by approximately 50% in humans. Rodent models of colon cancer also show reductions in tumor formation following NSAID treatment. NSAIDs are believed to act by inhibition of cyclooxygenase (COX-1 and COX-2). Our previous studies have shown a reduction in precancerous lesions in COX deficient Min mice. In the present study azoxymethane is being used to induce colon cancer in isogenic wild type and COX deficient mice. Azoxymethane initially induces precancerous aberrant crypt foci followed by adenocarcinomas. Azoxymethane treatment of mice genetically deficient in either COX-1 or COX-2, heterozygous for COX-1 or COX-2, or heterozygous for both isoforms, provides a method of studying COX dependent development of premalignant and malignant lesions. Our studies with the COX deficient mice should provide valuable information about the advantages of selectively inhibiting COX-1 or COX-2 vs the use of dual COX inhibitors.

流行病学数据表明，定期使用非甾体类抗炎药（NSAIDS）可将大肠癌的发生率降低约50％。 NSAID治疗后，结肠癌的啮齿动物模型还显示出肿瘤形成的减少。据信NSAID可以通过抑制环氧合酶（COX-1和COX-2）作用。我们先前的研究表明，Cox缺乏的最小小鼠中癌前病变的减少。在本研究中，二甲烷用于诱导等源性野生型和Cox缺乏小鼠的结肠癌。甲氧甲烷最初诱导癌前异常的隐窝灶，然后诱导腺癌。在COX-1或COX-2上遗传缺乏的小鼠甲氧甲烷治疗，COX-1或COX-2的杂合子，或两种同工型的杂合子，提供了一种研究依赖于COX依赖性和恶性病变的COX依赖性发展的方法。我们对COX缺陷小鼠的研究应提供有关选择性抑制COX-1或COX-2与使用双COX抑制剂的优势的有价值信息。