Larsson Karin, Jakobsson Per-Johan
Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Prostaglandins Other Lipid Mediat. 2015 Jul;120:161-5. doi: 10.1016/j.prostaglandins.2015.06.002. Epub 2015 Jun 20.
The bioactive lipid prostaglandin E2 (PGE2) is involved in several steps of carcinogenesis in some of the most common cancers, e.g. colon cancer, lung cancer, prostate cancer and breast cancer. Non-steroidal anti-inflammatory drugs (NSAIDs) that target cyclooxygenase (COX) activity, the first step of the PGE2 biosynthesis, has been found to reduce the incidence of colon cancer. Due to severe adverse effects on the gastrointestinal tract and the cardiovascular system, their use as chemopreventing agent has been hampered. Genetic deletion of microsomal prostaglandin E synthase-1 (mPGES-1), the enzyme responsible for the second step of the PGE2 biosynthesis, has resulted in reduced tumor progression in mouse models of colon cancer. Inhibition of mPGES-1 would potentially be beneficial to a great number of patients without the side effects associated with long-term treatment with traditional NSAIDs.
生物活性脂质前列腺素E2（PGE2）在一些最常见的癌症（如结肠癌、肺癌、前列腺癌和乳腺癌）的致癌过程的多个步骤中发挥作用。靶向环氧化酶（COX）活性（PGE2生物合成的第一步）的非甾体抗炎药（NSAIDs）已被发现可降低结肠癌的发病率。由于对胃肠道和心血管系统有严重的不良反应，它们作为化学预防剂的使用受到了阻碍。微粒体前列腺素E合酶-1（mPGES-1）是负责PGE2生物合成第二步的酶，在结肠癌小鼠模型中，其基因缺失导致肿瘤进展减缓。抑制mPGES-1可能对大量患者有益，且没有与传统NSAIDs长期治疗相关的副作用。
