The researchers examined the effect of inhibiting cyclooxygenase-2 (COX-2) activity in Barrett's esophagus cells.
They reported their results in the latest issue of the Journal of the National Cancer Institute.
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.
COX-2 is the rate-limiting enzyme involved in prostaglandin synthesis.
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 E2 (PGE2) enzyme immunoassay, respectively.
The investigators measured proliferation by Ki-67 staining.
PGE2 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).
Esophageal epithelial cells and fibroblasts expressed COX-2 messenger RNA.
The researchers found that, compared with control-treated cells, NS-398 decreased proliferation of Barrett's esophageal epithelial cells by 55% and decreased COX-2 activity.
| COX-2 inhibitor decreased Barrett's esophageal epithelial cell proliferation by 55%.
| Journal of the National Cancer Institute |
The addition of exogenous PGE2 reversed the antiproliferative effect of NS-398 on Barrett's esophageal epithelial cells.
Proinflammatory cytokines did not affect COX-2 activity in esophageal epithelial cells, but stimulated COX-2 activity in fibroblasts.
However, conditioned medium from unstimulated and stimulated fibroblasts increased COX-2 activity in esophageal epithelial cells.
Author Navtej S. Buttar, of the Mayo Graduate School of Medicine, Rochester, said on behalf of the group, "COX-2 is functionally active in Barrett's esophagus because treatment with the COX-2 inhibitor hinders proliferation of Barrett's esophageal epithelial cells in culture. However, proliferation is restored by treatment with prostaglandin."
"These results raise the possibility that inhibition of COX-2 may have chemopreventive potential for Barrett's esophagus," it was concluded.