Sasaki Yuka, Ochiai Tsubasa, Takamura Masaya, Kondo Yukihiro, Yokoyama Chieko, Hara Shuntaro
Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Tokyo, Japan.
Department of Urology, Nippon Medical School, Tokoyo, Japan.
Prostaglandins Other Lipid Mediat. 2017 Nov;133:49-52. doi: 10.1016/j.prostaglandins.2017.05.001. Epub 2017 May 12.
Prostacyclin (PGI) synthase (PGIS) and microsomal prostaglandin (PG) E synthase-1 (PGES-1) functionally couple with inducible cyclooxygenase-2 (COX-2) as their upstream enzymes to produce PGI and PGE, respectively. Non-steroidal anti-inflammatory drugs exert their pharmacological effects including antitumor effects by the inhibition of COX-2 and thereby suppress this PG biosynthesis. PGIS is abundantly expressed in vascular endothelial and smooth muscle cells and was shown to be critical for the regulation of platelet aggregation and vascular tone. In addition to its role in vascular regulation, PGIS was shown to be frequently down-regulated in several types of cancers, and the involvement of PGIS in carcinogenesis has been suggested. In this review, we summarize the current understanding of the roles of PGIS and PGIS-derived PGI in carcinogenesis.
前列环素（PGI）合酶（PGIS）和微粒体前列腺素（PG）E合酶-1（PGES-1）分别作为其上游酶与诱导型环氧化酶-2（COX-2）功能性偶联，以产生PGI和PGE。非甾体抗炎药通过抑制COX-2发挥其药理作用，包括抗肿瘤作用，从而抑制这种PG生物合成。PGIS在血管内皮细胞和平滑肌细胞中大量表达，并且已证明对调节血小板聚集和血管张力至关重要。除了其在血管调节中的作用外，PGIS在几种类型的癌症中经常被下调，并且有人提出PGIS参与致癌作用。在这篇综述中，我们总结了目前对PGIS和PGIS衍生的PGI在致癌作用中的作用的理解。
