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Gastroenterology. 2002 Apr;122(4):1101-12.

Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus.

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  • 1Department of Internal Medicine, Division of Gastroenterology and Hepatology, Mayo Graduate School of Medicine, Rochester, Minnesota, USA.

Abstract

BACKGROUND & AIMS:

Carcinogenesis in Barrett's esophagus (BE) is associated with an increased expression of cyclooxygenase (COX) 2. However, there has been no direct evidence that inhibition of COX-2 prevents cancer in BE. We studied the effect of MF-Tricyclic, a selective COX-2 inhibitor, on the development of BE and adenocarcinoma in a rat model.

METHODS:

Four weeks after esophagojejunostomy, 105 Sprague-Dawley rats were randomized to a chow containing MF-Tricyclic or Sulindac, or a placebo. Ninety-six (92%) rats completed the study and were sacrificed at 28 +/- 2 weeks. The animals were assessed for the presence of cancer, tumor volume, BE, degree of inflammation, and COX-2 expression and activity.

RESULTS:

MF-Tricyclic and Sulindac reduced the relative risk of development of esophageal cancer by 55% (95% confidence interval [CI] = 43%-66%, P < 0.008) and by 79% (95% CI = 68%-87%, P < 0.001), respectively, compared with controls. No significant differences were noted in the risk of esophageal cancer between the MF-Tricyclic and the Sulindac group (P = 0.34). The median tumor volume was not significantly different among the 3 groups (P = 0.081). Moderate to severe degree of inflammation was significantly more common (P = 0.005) in the control compared with the MF-Tricyclic and the Sulindac group; however, the prevalence of BE was not significantly different between groups (P = 0.98). Rats in the control group had higher tissue PGE2 level compared with the MF-Tricyclic and Sulindac groups (P = 0.038).

CONCLUSIONS:

Selective and nonselective COX-2 inhibitors can inhibit inflammation, COX-2 activity, and development of adenocarcinoma induced by reflux. This provides direct evidence that COX-2 inhibitors may have chemopreventive potential in BE.

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PMID:
11910360
[PubMed - indexed for MEDLINE]
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