title: A COX-2 inhibitor prevents the esophageal inflammation-metaplasia-adenocarcinoma sequence in rats.
abstract: 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.
authors.affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujimura
authors.forename: Itasu
authors.initials: I
authors.lastname: Ninomiya
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Miyashita
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kinami
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
authors.forename: Miwa
authors.initials: M
authors.lastname: Koichi
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002455:Cell Division; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D017931:DNA Primers; D015232:Dinoprostone / Q000096:biosynthesis; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000517:prevention & control*; D004941:Esophagitis / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D008297:Male; D008679:Metaplasia / Q000201:enzymology / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D017931:DNA Primers; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone