The team investigated whether inhibition of cyclooxygenase 2 (COX-2) with the selective inhibitor rofecoxib is important in chemoprevention of esophageal adenocarcinoma by decreasing cell proliferation.
The findings of the study were published in the July issue of Gastroenterology.
COX-2 is overexpressed in Barrett's esophagus and adenocarcinoma, and up-regulated by acid or bile salt exposure.
Biopsy specimens of esophagus, Barrett's esophagus, and duodenum were obtained at baseline from 12 patients.
These were compared with biopsy specimens obtained after 10 days of therapy with rofecoxib 25 mg, orally daily.
All patients were maintained asymptomatic on their proton pump inhibitor therapy throughout the study.
COX-2 expression, proliferating cell nuclear antigen (PCNA) expression (proliferation marker), and prostaglandin E2 (PGE2) biopsy content (marker of COX activity) were assessed. This was done by immunoblotting and enzyme immunoabsorbence assays.
At baseline, COX-2 expression was 3-fold higher in Barrett's esophagus than normal esophagus and duodenum.
| Rofecoxib reduced COX-2 expression in Barrett's by 77%.
| Gastroenterology |
However, after rofecoxib therapy, COX-2 expression in Barrett's esophagus decreased by 77%.
Similarly at baseline, PGE2 content was 2-fold higher in Barrett's esophagus than esophagus or duodenum.
The team found that, after rofecoxib therapy, PGE2 content decreased in Barrett's esophagus by 59%.
At baseline, PCNA expression was also 2-fold higher in Barrett's esophagus than squamous esophagus and duodenum.
Rofecoxib therapy reduced PCNA expression in Barrett's esophagus by 63%.
Baljeet S. Kaur, of the Veterans Affairs Palo Alto Health Care System, Palo Alto, California, said on behalf of fellow authors, "Rofecoxib 25 mg orally once daily reduces COX-2 expression, PGE2 release, and cell proliferation in Barrett's esophagus."
"Together with acid suppressive therapy, rofecoxib may be a promising chemoprevention agent against dysplasia and esophageal adenocarcinoma," it was concluded.