Myung Seung-Jae, Kim In-Hwa
Division of Gastroenterology, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Korea.
Korean J Gastroenterol. 2008 May;51(5):274-9.
Colon cancer is one of the major leading causes of cancer-related deaths in the Western countries. In Korea, the incidence of colon cancer is increasing due to changes in environment and lifestyle such as diet. Chemoprevention strategy using non-steroidal anti-inflammatory drugs (NSAIDs) has been under intensive clinical and epidemiological research as these drugs suppress colorectal cancer. The best known targets of NSAIDs are cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins (PGs) and thromboxane. Among these PGs, prostaglandin E2 (PGE2) can promote tumor growth by binding its receptors and activating signal pathways which control cell proliferation, migration, apoptosis, and angiogenesis. Therefore, COX inhibition is promising approach for chemoprevention of colorectal cancer. However, the prolonged use of COX-2 inhibitors is associated with unacceptable cardiovascular side effects. Thus, new targets involved in PGs metabolism are under investigation. 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key metabolic enzyme of PGE2, was up-regulated in normal colonic epithelium, but decreased in colon cancer. Recent findings suggest that 15-PGDH is involved in the neoplastic progression of initiated colonic epithelial cells. Also, new players related with PGs metabolism including prostaglandin transporter (PGT) and microsomal prostaglandin E synthase (mPGES) were reported to play a role in colorectal cancer development. This review presents current knowledge about the role of prostaglandins and associated proteins in colorectal cancer development and progression.
结肠癌是西方国家癌症相关死亡的主要原因之一。在韩国，由于环境和生活方式的改变，如饮食变化，结肠癌的发病率正在上升。使用非甾体抗炎药（NSAIDs）的化学预防策略一直是临床和流行病学的重点研究对象，因为这些药物可以抑制结直肠癌。NSAIDs最著名的靶点是环氧合酶（COX），它将花生四烯酸转化为前列腺素（PGs）和血栓素。在这些PGs中，前列腺素E2（PGE2）可以通过与其受体结合并激活控制细胞增殖、迁移、凋亡和血管生成的信号通路来促进肿瘤生长。因此，COX抑制是预防结直肠癌的一种有前景的方法。然而，长期使用COX-2抑制剂会带来不可接受的心血管副作用。因此，参与PGs代谢的新靶点正在研究中。15-羟基前列腺素脱氢酶（15-PGDH）是PGE2的关键代谢酶，在正常结肠上皮中上调，但在结肠癌中降低。最近的研究结果表明，15-PGDH参与了起始结肠上皮细胞的肿瘤进展。此外，据报道，与PGs代谢相关的新成员，包括前列腺素转运体（PGT）和微粒体前列腺素E合酶（mPGES），在结直肠癌的发展中发挥作用。本文综述了前列腺素及其相关蛋白在结直肠癌发生发展中的作用的现有知识。
