Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice.

Two isoforms of cyclooxygenase (COX) are known, and to date most studies have implicated COX-2, rather than COX-1, as the isoform involved in colon carcinogenesis. In the present study, we show that homologous disruption of either Ptgs-1 or Ptgs-2 (genes coding for COX-1 or COX-2, respectively) reduced polyp formation in Min/+ mice by approximately 80%. Only COX-1 protein was immunohistochemically detected in normal intestinal tissue, whereas both COX-1 and variable levels of COX-2 protein were detected in polyps. Prostaglandin E2 was increased in polyps compared with normal tissue, and both COX-1 and COX-2 contributed to the PGE2 produced. The results indicate that COX-1, as well as COX-2, plays a key role in intestinal tumorigenesis and that COX-1 may also be a chemotherapeutic target for nonsteroidal anti-inflammatory drugs.

已知有两种环氧化酶（COX）异构体，到目前为止，大多数研究表明在结肠癌发生过程中起作用的是COX - 2而非COX - 1。在本研究中，我们发现Ptgs - 1或Ptgs - 2（分别为编码COX - 1和COX - 2的基因）的同源基因破坏使Min/+小鼠的息肉形成减少了约80%。在正常肠道组织中仅通过免疫组化检测到COX - 1蛋白，而在息肉中可检测到COX - 1和不同水平的COX - 2蛋白。与正常组织相比，息肉中的前列腺素E2增加，并且COX - 1和COX - 2都对产生的前列腺素E2有贡献。结果表明，COX - 1和COX - 2在肠道肿瘤发生中都起关键作用，并且COX - 1也可能是非甾体抗炎药的化疗靶点。