Rofecoxib inhibits cyclooxygenase 2 expression and activity and reduces cell proliferation in Barrett's esophagus.
OBJECTIVE
Cyclooxygenase 2 (COX-2) is overexpressed in Barrett's esophagus and adenocarcinoma and up-regulated by acid or bile salt exposure. COX-2 inhibition with the selective inhibitor rofecoxib may be important in chemoprevention of esophageal adenocarcinoma by decreasing cell proliferation.


METHODS
Biopsy specimens of esophagus, Barrett's esophagus, and duodenum were obtained at baseline from 12 patients and 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 by immunoblotting and enzyme immunoabsorbence assays.


RESULTS
At baseline, COX-2 expression was 3-fold higher in Barrett's esophagus than esophagus and duodenum (P < 0.05). After rofecoxib therapy, COX-2 expression in Barrett's esophagus decreased by 77% (P < 0.005). Similarly at baseline, PGE2 content was 2-fold higher in Barrett's esophagus than esophagus or duodenum. After rofecoxib therapy, PGE2 content decreased in Barrett's esophagus by 59% (P < 0.005). At baseline, PCNA expression was also 2-fold higher in Barrett's esophagus than squamous esophagus and duodenum (P < 0.005). After rofecoxib therapy, PCNA expression in Barrett's esophagus decreased by 62.5% (P < 0.005).


CONCLUSIONS
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.
Kaur
Baljeet S
BS
Gastroenterology Section, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA.
Khamnehei
Niloufar
N
Iravani
Mohamed
M
Namburu
Sai S
SS
Lin
Otto
O
Triadafilopoulos
George
G
D000368:Aged; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases; D013450:Sulfones
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone