前列腺素类物质在胃肠道肿瘤发病机制中的作用

环氧合酶(cyclooxygenase,COX)是催化花生四烯酸转化为前列腺素过程中的一个关键限速酶.哺乳动物的COX有两种形式,即COX-1和COX-2.COX-1在大多数组织中都有表达,其催化产生的前列腺素参与维持机体正常的生理机能.而COX-2是一种诱导酶,在细胞受到各种刺激时,如组织损伤、炎症或细胞恶性转化时表达增强.近年来大量研究表明,COX-2通过前列腺素途径除参与炎症反应外,还与胃肠道肿瘤发生、发展关系密切,COX-2在结直肠癌、胃癌和食管癌中的作用主要是通过PGE2等前列腺素来调节的,目前的研究认为前列腺素对肿瘤的促进作用主要牵涉下列分子机制:促进细胞增殖、抑制凋亡、促进侵袭和转移、刺激血管生成和诱导免疫抑制.本文就前列腺素类物质在胃肠道肿瘤发病机制中的研究进展作一综述.

Role of prostaglandins in pathogenesis of gastrointestinal cancer

There are 2 cyclooxygenase (COX) isoforms commonly referred to COX-1 and COX-2 for the temporal order of their discovery. Although both COX-1 and COX-2 are up-regulated in a variety of circumstances, normally, COX-1 is constitu- tively expressed in a broad range of cells and tis- sues. COX-1 expression remains constant under most physiologic or pathologic conditions, and COX-1-derived prostaglandins are considered to play a role in many normal physiologic pro- cesses. COX-2, by contrast, is an immediate- early response gene normally absent from most cells but highly inducible in response to inflam- matory stimuli, including endotoxin, cytokines, hormones, and tumor promoters. Prostaglandins derived from COX-1 and COX-2 are involved in a variety of physiologic and pathologic pro- cesses in the gastrointestinal tract. Recent efforts to identify the molecular mechanisms by which COX-2-derived prostanoids exert their proneo- plastic effects have provided a rationale for the possible use of non-steroidal anti-inflammatory drugs alone or in combination with conventionalor experimental anticancer agents for the treat- ment or prevention of gastrointestinal cancers.