Oyama Katsunobu, Fujimura Takashi, Ninomiya Itasu, Miyashita Tomoharu, Kinami Shinichi, Fushida Sachio, Ohta Tetsuo, Koichi Miwa
Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
Carcinogenesis. 2005 Mar;26(3):565-70. doi: 10.1093/carcin/bgh340. Epub 2004 Nov 25.
Barrett's esophagus (BE) and esophageal adenocarcinoma (ADC) is associated with reflux of duodenal contents. Cyclooxygenase (COX)-2 is over-expressed in BE and ADC, and supposedly contributes to esophageal carcinogenesis. The aim of this study is to investigate what effect a COX-2 inhibitor has on esophageal adenocarcinogenesis in rats. A series of 90 rats underwent a duodenoesophageal reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other was given experimental chow containing celecoxib (celecoxib group). The animals were sacrificed sequentially, at the 10th, 20th, 30th and, finally, 40th week after surgery, and their esophagi were examined. In the control group, esophagitis, columnar-lined epithelium (CLE) and ADC were first observed at the 10th week, 20th week and 30th week, respectively. Their incidences sequentially increased and at the 40th week reached 100, 89 and 47%, respectively. In the celecoxib group, the esophagitis was mild and the incidence of CLE was significantly lower at each week (P < 0.001), compared with the control group, and ADC was not observed throughout the experiment (P < 0.05). COX-2 expression was observed predominantly in the stroma of inflamed esophageal epithelia, and up-regulated at the 10th and 20th week (P < 0.05, respectively). PGE2 level and proliferative activity were also up-regulated in both groups, but they were lower in the celecoxib group than in the control group (P < 0.05). Apoptosis was observed to increase with celecoxib treatment (P < 0.05). Celecoxib is effective in preventing CLE and ADC by suppressing esophagitis in rats.
巴雷特食管（BE）和食管腺癌（ADC）与十二指肠内容物反流有关。环氧化酶（COX）-2在BE和ADC中过度表达，据推测其与食管癌发生有关。本研究的目的是探讨COX-2抑制剂对大鼠食管腺癌发生有何影响。90只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），另一组给予含塞来昔布的实验饲料（塞来昔布组）。在手术后第10周、20周、30周，最后在第40周依次处死动物，并检查其食管。在对照组中，食管炎、柱状上皮化生（CLE）和ADC分别在第10周、20周和30周首次观察到。它们的发生率依次增加，在第40周分别达到100%、89%和47%。在塞来昔布组中，食管炎较轻，与对照组相比，各周CLE的发生率均显著降低（P<0.001），且在整个实验过程中未观察到ADC（P<0.05）。COX-2表达主要在炎症食管上皮的基质中观察到，并在第10周和第20周上调（分别为P<0.05）。两组中前列腺素E2水平和增殖活性也上调，但塞来昔布组低于对照组（P<0.05）。观察到塞来昔布治疗可使细胞凋亡增加（P<0.05）。塞来昔布通过抑制大鼠食管炎对预防CLE和ADC有效。
