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

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.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Buttar NS,Wang KK,Leontovich O,Westcott JY,Pacifico RJ,Anderson MA,Krishnadath KK,Lutzke LS,Burgart LJ

doi

10.1053/gast.2002.32371

keywords:

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

1101-12

issue

4

eissn

0016-5085

issn

1528-0012

pii

S0016508502476354

journal_volume

122

pub_type

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