Deficiency of COX 1 or 2 on chemical intestinal cancer

流行病学数据表明，定期使用非类固醇抗炎药(NSAIDs)可将人类结直肠癌的发病率降低约50%。非甾体抗炎药治疗后，结肠癌的啮齿动物模型也显示肿瘤形成减少。非甾体抗炎药被认为是通过抑制环氧合酶(COX-1和COX-2)起作用的。我们之前的研究表明，COX基因缺陷的Min小鼠的癌前病变减少。在目前的研究中，偶氮甲烷被用来诱导同基因野生型和COX缺陷小鼠的结肠癌。偶氮甲烷最初会导致癌前病变，继而是腺癌。对COX-1或COX-2基因缺陷、COX-1或COX-2杂合子或这两种异构体杂合子的小鼠进行偶氮甲烷治疗，提供了一种研究癌前和恶性病变中COX依赖发展的方法。 我们对COX基因缺陷小鼠的研究应该为选择性抑制COX-1或COX-2与使用双重COX抑制剂的优势提供有价值的信息。

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.