Journal Article

A COX-2 inhibitor prevents the esophageal inflammation–metaplasia–adenocarcinoma sequence in rats

Katsunobu Oyama, Takashi Fujimura, Itasu Ninomiya, Tomoharu Miyashita, Shinichi Kinami, Sachio Fushida, Tetsuo Ohta and Miwa Koichi

in Carcinogenesis

Volume 26, issue 3, pages 565-570
Published in print March 2005 | ISSN: 0143-3334
Published online March 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh340
A COX-2 inhibitor prevents the esophageal inflammation–metaplasia–adenocarcinoma sequence in rats

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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.

Keywords: ADC, adenocarcinoma; BCH, basal cell hyperplasia; BE, Barrett's esophagus; CLE, columnar-lined epithelium; COX, cyclooxygenase; PGE2, prostaglandin E2; RT, regenerative thickening.

Journal Article.  4723 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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