A selective cyclooxygenase‐2 inhibitor prevents inflammation‐related squamous cell carcinogenesis of the forestomach via duodenogastric reflux in rats

Abstract

Duodenal reflux causes inflammation-related squamous cell carcinogenesis in the forestomach of rats without any carcinogens. The aim of this study was to investigate the efficacy of a selective cyclooxygenase (COX)-2 inhibitor, meloxicam, in preventing this carcinogenesis. A series of 188 rats underwent a surgical duodenogastric reflux procedure and were divided into 2 groups. One group was given commercial chow (control group), and the other was given experimental chow containing meloxicam (0.3 mg/kg body weight/day) (meloxicam group). The animals were sequentially sacrificed at Weeks 20, 30, 40, 50, and 60 after surgery. The forestomach was examined for the presence of carcinoma, the incidence of reflux-related morphological changes, COX-2 expression, and its activity. At Week 60, squamous cell carcinoma developed in 8 of 21 animals (38%) in the control group, but none of 20 (0%) in the meloxicam group (P<.05). In addition, basal cell dysplasia developed in 19 of 21 (90%) animals in the control group, but only 4 of 20 (20%) in the meloxicam group (P<.01). COX-2 immunoreactivity was predominantly detected in macrophages in the epithelial stroma. Compared with nonsurgical rats, RNA expression of COX-2 in the epithelium was up-regulated, reaching peak at an early stage of Week 20 in both groups (P<.005). The expression of microsomal prostaglandin E synthase-1 was lower in the meloxicam group than in the control group. PGE2 production was significantly suppressed throughout the experiment in the meloxicam group compared with the control group (P<.005). Meloxicam was effective in preventing reflux-induced squamous cell carcinogenesis via an inflamed squamous epithelium.