Rofecoxib inhibits cyclooxygenase 2 expression and activity and reduces cell proliferation in Barrett's esophagus

罗非昔布 环氧合酶 巴雷特食管 食管 细胞生长 化学 内科学 医学 癌症研究 生物化学 腺癌 癌症
作者
Baljeet S. Kaur,Niloufar Khamnehei,Mohamed Iravani,Sai S. Namburu,Otto S. Lin,George Triadafilopoulos
出处
期刊:Gastroenterology [Elsevier]
卷期号:123 (1): 60-67 被引量:138
标识
DOI:10.1053/gast.2002.34244
摘要

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.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.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).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.
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