Chemoprevention of gastric cancer by celecoxib in rats.
نویسندگان
چکیده
BACKGROUND Overexpression of cyclooxygenase 2 (COX-2) is frequently detected in gastric cancer and is believed to play a crucial role in gastric carcinogenesis. AIM We examined the chemopreventive effect of a COX-2 inhibitor in an animal model of stomach carcinogenesis. METHODS Eighty six male Wistar rats were divided into six different treatment groups: group A, water alone (n = 5); group B, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG 100 micro g/ml) (n = 16); group C, indomethacin (3 mg/kg/day) (n = 16); group D, celecoxib (5 mg/kg/day) (n = 17); group E, celecoxib (10 mg/kg/day) (n = 16); and group F, celecoxib (20 mg/kg/day) (n = 16). Group B-F animals were treated with 10% sodium chloride (in the initial six weeks) and MNNG in drinking water to induce adenocarcinoma in the stomach. All animals received treatment for 40 weeks, and were sacrificed after death or at 48 weeks. Gastric neoplasm was evaluated by histology. RESULTS The incidences of gastric cancer were 0% in group A, 75% in group B, 68.8% in group C, 70.6% in group D, 18.8% in group E, and 31.3% in group F (p = 0.002, ANOVA). Compared with MNNG controls, treatment with celecoxib 10 mg/kg/day also showed lower tumour multiplicity (0.19 (0.40) v 1.00 (0.73); p = 0.004) and lower mean tumour volume (2.4 v 2805 mm(3); p = 0.02). Although tumours had significantly higher COX-2 expression than their adjacent normal tissues (p<0.02), there was no significant difference in COX-2 levels among tumours in the different treatment groups. The lowest tumour prostaglandin E(2) level was found in the indomethacin treated group, suggesting that the chemopreventive effect of celecoxib may be mediated by a COX independent pathway. CONCLUSION While treatment with indomethacin had no significant effect on tumour development, treatment with celecoxib reduced gastric cancer incidence and growth in rats.
منابع مشابه
Different cell kinetic changes in rat stomach cancer after treatment with celecoxib or indomethacin: implications on chemoprevention.
AIM Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer development in Wistar rats. This chemopreventive effect appeared to be independent of COX-2 and prostaglandin (PG) E2 suppression since the lowest PGE2 was obtained in indomethacin gr...
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Background: Overexpression of cyclooxygenase 2 (COX-2) is frequently detected in gastric cancer and is believed to play a crucial role in gastric carcinogenesis. Aim: We examined the chemopreventive effect of a COX-2 inhibitor in an animal model of stomach carcinogenesis. Methods: Eighty six male Wistar rats were divided into six different treatment groups: group A, water alone (n = 5); group B...
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ورودعنوان ژورنال:
- Gut
دوره 53 2 شماره
صفحات -
تاریخ انتشار 2004