摘要
目的:本实验通过观察舒林酸对凋亡调控基因的影响,初步探讨舒林酸防治肿瘤作用可能存在的分子机制。方法:利用二甲肼诱发的实验性大肠癌小鼠模型,采用免疫组化染色的方法,分别标记p53、Bcl-2和Bax阳性细胞,分阶段地动态观察舒林酸对各种蛋白表达的影响。结果:预防组、治疗组的p53阳性率与模型组差别均有统计学意义(P均<0.01);随实验观察时间延长,p53和Bax呈逐渐升高趋势,而Bcl-2和Bcl-2/Bax分别在第3和第2阶段达到峰值后呈下降趋势。至实验结束时,预防组p53、Bcl-2以及Bcl-2/Bax比值均低于模型组(除p53外,P均<0.05),而治疗组与模型组仅Bax之间差别具有统计学意义(P<0.01)。结论:舒林酸通过抑制突变型p53和Bcl-2的表达,诱导细胞凋亡,从而抑制肿瘤形成和发展。
Objective： To observe the effect of Sulindac on changes of the apoptosis regulating genes in different stages of the tumor formation, and probe the possible antieareinogenie molecular mechanism of sulindac. Methods： The expressions of p53, Bcl-2 and Bax on different stages of tumor formation in mice models of 1, 2-dimethylhydrazin （DMH） -induced colon carcinogenesis were determined by immunohistoehemical staining. Results： During the formation of coloreetal tumorigenesis, along with the aggravation of atypical hyperplasia, the density of p53 and Bax gradually rose （P〈0.01）, but Bcl-2 and Bcl-2/Bax ratio decreased after reached maximum value at the third or the second stage. At the end of the experiment, the density of p53, Bcl-2 and Bel-2/Bax ratio were higher in prevention group than that in model group （all P〈0.01 except p53）; but in the treatment group, only Bax was significantly lower than that in the model group （P〈0.01）. Conclusion： During the course of colon carcinogenesis, sulindae induces the apoptosis of colon epithelial cells by down-regulating the expression of mutant p53 and Bcl-2 to inhibit the development of colon cancer.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2006年第8期469-472,共4页
Chinese Journal of Clinical Oncology
基金
天津市自然科学基金项目资助(编号:973611311)
关键词
舒林酸
大肠癌
P53
凋亡
Sulindac Colorectal tumor p53 Apoptosis
