Antiangiogenic effect of a highly selective cyclooxygenase-2 inhibitor on gastric ulcer healing in rats.
Selective cyclooxygenase-2 (COX-2) inhibitors have been shown to produce fewer gastrointestinal adverse reactions when compared with conventional nonselective nonsteroidal anti-inflammatory drugs and they suppress angiogenesis in tumors. The purpose of the present study was to investigate the effects of highly selective COX-2 inhibitor on angiogenesis and protein expression of angiogenic factor during gastric ulcer healing. Gastric ulcers were induced in male Sprague-Dawley rats by a luminal application of acetic acid solution. Rofecoxib, a selective COX-2 inhibitor, was administered at a dose of 10 mg/kg/day by gastric intubation for 14 successive days. The ulcer size was measured at different time intervals after ulcer induction. The microvessels that were immunohistologically positive for von Willebrand factor within the ulcer bed were counted. The protein levels of basic fibroblast growth factor (bFGF) and concentration of prostaglandin E(2) (PGE(2)) in the ulcer tissues were analyzed with Western blotting and immunoassay methods, respectively. The results demonstrated that rofecoxib treatment significantly increased the ulcer size at days 6, 10, and 15. It decreased the number of microvessels, bFGF protein expression, and PGE(2) level in the ulcer base at day 6. The findings that highly selective COX-2 inhibitor delayed ulcer healing in rats and impaired angiogenesis in the ulcer base raise cautions regarding the use of COX-2 inhibitors in patients with gastric ulcers.
Guo
Jin Sheng
JS
Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong.
Cho
Chi Hin
CH
Lam Liu
Edgar Shiu
ES
Choy
Hau Tim
HT
Wang
Ji Yao
JY
Leung Koo
Marcel Wing
MW
D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D015232:Dinoprostone / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects*; D007783:Lactones / Q000009:adverse effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000473:pathology; D013450:Sulfones
D020533:Angiogenesis Inhibitors; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D016222:Fibroblast Growth Factor 2; D015232:Dinoprostone