Deficiency of COX 1 or 2 on chemical intestinal cancer

流行病学数据表明，定期使用非甾体抗炎药（NSAID）可将人类结直肠癌的发病率降低约50%。结肠癌的啮齿动物模型也显示NSAID治疗后肿瘤形成减少。据信NSAID通过抑制环氧合酶（考克斯-1和考克斯-2）发挥作用。我们以前的研究表明，在考克斯缺陷Min小鼠的癌前病变减少。在目前的研究中，氧化偶氮甲烷被用来诱导结肠癌的同基因野生型和考克斯缺陷小鼠。氧化偶氮甲烷首先诱导癌前异常隐窝灶，然后是腺癌。用氧化偶氮甲烷处理考克斯-1或考克斯-2遗传缺陷、考克斯-1或考克斯-2杂合或两种亚型杂合的小鼠，提供了一种研究癌前病变和恶性病变的考克斯依赖性发展的方法。 我们对考克斯缺陷小鼠的研究应该提供关于选择性抑制考克斯-1或考克斯-2与使用双重考克斯抑制剂的优势的有价值的信息。

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.