Oyama Katsunobu, Fujimura Takashi, Ninomiya Itasu, Miyashita Tomoharu, Kinami Shinichi, Fushida Sachio, Ohta Tetsuo
Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University.
Nihon Shokakibyo Gakkai Zasshi. 2007 Aug;104(8):1183-91.
The aim of this study is to investigate the cyclooxygenase (COX)-2 expression in esophageal epithelium of rat duodenoesophageal reflux model and the effect of a selective COX-2 inhibitor on esophageal adenocarcinogenesis in rats. A series of rats underwent a duodenoesophageal reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other group was given experimental chow containing nimesulide, a selective COX-2 inhibitor (nimesulide group). The animals were sacrificed sequentially after surgery and esophageal examinations were performed. In the control group, esophagitis, Barrett's esophagus (BE) and adenocarcinoma (EAC) were observed, and the frequency of these conditions increased with time. COX-2 expression, PGE(2) level and proliferative activity were up-regulated, predominantly in the inflamed esophageal epithelia, from the 10(th) week. In the nimesulide group, the esophagitis was mild and the frequency of BE was significantly lower than the control group, while EAC was not observed throughout the experiment. PGE(2) level and proliferative activity were lower in the nimesulide group than in the control group. COX-2 may play an important role in esophageal carcinogenesis through the activation of the inflammation-metaplasia-adenocarcinoma sequence. Nimesulide is effective in preventing BE and EAC by suppressing COX-2 activity.
本研究旨在探讨大鼠十二指肠食管反流模型食管上皮中环氧化酶(COX)-2的表达,以及选择性COX-2抑制剂对大鼠食管腺癌发生的影响。一系列大鼠接受了十二指肠食管反流手术,并分为两组。一组给予普通饲料(对照组),另一组给予含选择性COX-2抑制剂尼美舒利的实验饲料(尼美舒利组)。术后依次处死动物并进行食管检查。在对照组中,观察到食管炎、巴雷特食管(BE)和腺癌(EAC),且这些情况的发生率随时间增加。从第10周起,COX-2表达、PGE(2)水平和增殖活性上调,主要在炎症性食管上皮中。在尼美舒利组中,食管炎较轻,BE的发生率显著低于对照组,而在整个实验过程中未观察到EAC。尼美舒利组的PGE(2)水平和增殖活性低于对照组。COX-2可能通过激活炎症-化生-腺癌序列在食管癌变中起重要作用。尼美舒利通过抑制COX-2活性有效预防BE和EAC。