The effect of selective cyclooxygenase-2 inhibition in Barrett's esophagus epithelium: an in vitro study

Background: Individuals with Barrett's esophagus, in which the normal squamous esophageal epithelium is replaced with a columnar mucosa, are at increased risk for esophageal adenocarcinoma. Mucosal injury may be involved in the progression to neoplasia via the synthesis of prostaglandins and other mediators of inflammation. Cyclooxygenase (COX)-2 is the rate-limiting enzyme involved in prostaglandin synthesis. We examined the effect of inhibiting COX-2 activity in Barrett's esophageal cells. Methods: Primary esophageal epithelial and fibroblast cell cultures were established from endoscopic biopsy specimens from 20 consecutive patients with Barrett's esophagus. COX-2 expression and activity were determined on pooled cell cultures by reverse transcription--polymerase chain reaction and prostaglandin [E.sub.2] (PG[E.sub.2]) enzyme immunoassay, respectively. Proliferation was measured by Ki-67 staining. PG[E.sub.2] levels were determined in supernatants from epithelial cells treated with the selective COX-2 inhibitor NS-398, proinflammatory cytokines (interleukin 1[beta] and tumor necrosis factor-[alpha]), and conditioned medium from fibroblast cultures (both unstimulated and stimulated with proinflammatory cytokines). Results: Esophageal epithelial cells and fibroblasts expressed COX-2 messenger RNA. Compared with control-treated cells, NS-398 decreased proliferation of Barrett's esophageal epithelial cells by 55% (95% confidence interval = 47.1% to 63.8%; P