罗非昔布对大鼠结肠肿瘤细胞外信号调节蛋白激酶表达的影响

Effects of ERK/pERK expressed on rat colon neoplasm by rofecoxib.

目的 研究选择性COX 2抑制剂罗非昔布对大鼠结肠肿瘤的防治作用及对肿瘤组织细胞外信号调节蛋白激酶(ERK/pERK)表达的影响。方法 利用二甲肼(DMH)诱导Wister大鼠结直肠肿瘤发生;用5mg/kg罗非昔布给大鼠灌胃,观察药物对大鼠结直肠肿瘤的预防和治疗作用及对肿瘤组织ERK/pERK表达的影响。结果 DMH能诱发大鼠结直肠腺瘤及腺癌,2 2周末,罗非昔布预防组腺瘤发生率为5 0 %,对照组腺瘤发生率为10 0 %;罗非昔布预防组及对照组大鼠平均每只腺瘤数分别为1 . 66±0 . 5 7与2 83±1 16,二者有显著差异(P <0 . 0 5 )。2 4周末,罗非昔布预防组腺癌发生率为5 0 %,对照组发生率为83 . 3 %;预防组及对照组腺癌分别为1 . 3 3±0 . 5 8与2 . 40±0 . 89,二者有显著差异(P <0 . 0 5 )。大鼠结直肠肿瘤组织pERK水平较正常结肠组织明显升高,腺瘤和腺癌组织pERK的表达无明显差异;罗非昔布作用组pERK表达明显下调。结论 罗非昔布不仅能预防化学致癌剂诱发大鼠结直肠腺瘤发生,还能减少腺癌发生;这种作用可能部分通过抑制结直肠肿瘤pERK表达实现。

Objective To study the effect of rofecoxib on colon neoplasm of rat induced by DMH and ERK/pERK expression.Methods Rat colon neoplasm were induced by 1,2-dimethylhydrazine(DMH)and rofecoxib(5mg/kg)were administrated to investigate its effect on tumor growth.Expression of ERK and pERK in normal colon mucosa,colon adenoma or adenocarcinoma were detected by immunohistochemistry.Results Colon adenomas and carcinomas were successfully induced by DMH in this study.At the end of 22 weeks,adenomas were found in all six control animals(100%) injected with DMH alone.However,adenomas were found in 3 of 6 experimental animals(50%) treated with DMH plus rofecoxib.The average numbers of adenomas in rofecoxib and control groups showed significant deference(2.83±1.16 vs 1.66±0.57,P<0 05).At the end of 24 weeks,carcinomas were found in 5 of 6 animals(83.3%)injected with DMH alone and found in 3 of 6 animals(50%)treated with DMH plus rofecoxib.Rofecoxib significantly decrease the average numbers of carcinomas(2.40±0.89 vs 1.33±0.58,P<0 05).The level of pERK expressed in rat colon neoplasm was higher than that of normal epithelium.There was little difference in ERK activity in adenoma compared with carcinoma.However,compared with untreated groups,pERK were decreased in colonic neoplasms treated with rofecoxib.Conclusion Rofecoxib not only prevent form of rat colon adenoma induced by DMH,but also reduced incidence of colon carcinoma.These effects were obtained partly though MAPK(ERK) pathway.