特异性环氧合酶-2抑制剂预防胃癌的实验研究

Chemoprevention of gastric cancer by specific cyclooxygenase-2 inhibitor in rats

目的 探讨特异性环氧合酶 (COX) 2抑制剂塞来昔布 (Celecoxib)对化学致癌剂 (N 甲基 N′ 硝基 亚硝基胍 ,MNNG)诱导的胃癌发生的影响。方法 86只二级雄性Wistar大鼠分为A、B、C、D、E、F共 6组。A组 (5只 ) :自由饮用蒸馏水不作特殊处理 ;B组 (16只 ) :仅饮用含MNNG 10 0 μg/ml的蒸馏水 ;C组 (16只 ) :每天给予吲哚美辛 3mg/kg ;D组 (17只 ) :每天给予塞来昔布 5mg/kg ;E组 (16只 ) :每天给予塞来昔布 10mg/kg ;F组 (16只 ) :每天给予塞来昔布 2 0mg/kg。B～F组动物给予 10 %氯化钠(实验初 6周 )和饮水中加用MNNG(10 0 μg/ml) ,以诱导胃癌 ,持续 4 0周 ,第 4 8周时处死动物。观察、比较各组动物大体及组织学变化。结果 86只大鼠实验期间自然死亡 2 6只 (30 % ) ,余 6 0只完成实验研究。A、B、C、D、E、F组动物胃癌发生率分别为 0 % (0 / 5 )、75 .0 % (12 / 16 )、6 8.8% (11/ 16 )、70 .6 % (12 /17)、18.8% (3/ 16 )和 31.3% (5 / 16 )。各组动物胃癌发生率 (P =0 .0 0 2 )、多发数目 (P =0 .0 0 1)、肿瘤体积 (P =0 .0 0 9)差异有显著性。与B组相比 ,E组胃癌发生率 (P =0 .0 0 4 )、多发数目 (P =0 .0 0 6 )和肿瘤体积 (P =0 .0 2 )显著降低。C组与B组相比差异无显著性。

Objective To examine the chemo-preventive effect of cyclooxygenase-2(COX-2) inhibitor (celecoxib) in an animal model of stomach carcinogenesis. Methods Eighty-six male Wistar rats were divided into six groups. The rats were given water alone (group A, n=5), N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) (group B, n=16), 3 mg/kg of indomethacin daily (group C, n=16), 5 mg/kg of celecoxib daily (group D, n=17), 10 mg/kg of celecoxib daily (group E, n=16) or 20 mg/kg of celecoxib daily (group F, n=16). The animals in group B to F were given 10% sodium chloride (in the initial 6 weeks) and drinking water containing MNNG (100 μg/ml) to induce gastric adenocacinoma. All animals received treatment for 40 weeks, and were sacrificed after death or at week 48. Gastric tumor was evaluated histologically. Results Among 86 rats, 26 rats died, and 60 rats completed the experiment. The incidences of gastric cancer were found 0 (0%) in group A, 12 (75.0%) in group B, 11 (68.8%) in group C, 12 (70.6%) in group D, 3(18.8%) in group E, and 5(31.3%) in group F. There were significant differences in tumor incidence (P=0.002), multiplicity (P=0.001) and volume (P=0.009) among different groups. When compared with group B, the group E had the greatest reduction in tumor incidence (P=0.004), tumor multiplicity ( P=0.006) and mean tumor volume (P=0.02). Treatment with indomethacin had no significant effect on tumor development. Conclusion While treatment with indomethacin had no significant effect on tumor development, treatment with celecoxib reduced gastric cancer incidence and growth in rats.