叶酸对二甲肼诱发小鼠大肠癌干预及其机制的研究  

Prevention effect of folic acid in a mouse model of colorectal cancer induced by dimethylhydrazine

作　　者：陆嵘[1] 王霞[1] 房静远[1] 

机构地区：[1]上海交通大学医学院附属仁济医院消化科上海市消化疾病研究所,上海200001

出　　处：《中华肿瘤防治杂志》2009年第9期645-648,共4页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的:观察在二甲肼(dimethyl-hydrazine,DMH)诱导小鼠大肠癌的过程中,通过叶酸进行化学干预能否预防肿瘤的发生。方法:以DMH诱发ICR小鼠大肠癌,在诱癌过程中用叶酸进行干预,观察其对肿瘤发生率的影响。定量PCR检测癌基因c-myc转录水平。甲基化特异性PCR(MSP)分析癌基因c-myc启动子区甲基化情况。结果:补充叶酸使小鼠大肠癌的发生率由95%降低至45%;MSP分析9例c-myc表达升高的DMH造模组中有4例发现肿瘤组织DNA启动子区低甲基化,并且发现这4只小鼠的叶酸水平为(71.65±7.04)ng/mL,低于该组其他小鼠(85.75±11.78)ng/mL,P<0.05。结论:通过补充叶酸能有效降低DMH诱发小鼠大肠癌的发生率,其预防肿瘤发生的作用机制与其对基因表达的表观遗传调控有关。OBJECTIVE：To investigate the effects of folio acid on prevention of colorectal cancer in mice induced by dimethylhydrazine （DMH）. METHODS.. The colorectal neoplasms were induced with DMH in ICR mice and the different doses of folic acid were administered,then the prevention of colorectal neoplasms was examined. The transcription levels of c-myc gene were detected by real-time RT PCR. The promoter methylation states of c-myc gene were determined by methylation specific PCR （MSP）. RESULTS：The mice were treated in a chemopreventive manner with folic acid, 45% mice developed colorectal cancer, whereas 95% control-treated mice developed colorectal cancer. Up regulated expression of the c myc gene in 9 out of 19 in cancerous tissues in the DMH-treated group; moreover, promoter hypomethylation of the c-myc gene was observed in 4 of these 9 mice. Furthermore, the mean serum FA concentration in these four mice was significantly lower than that in the other mice in this group （（71.65 ± 7.04） ng/mL vs （85.75± 11.78） ng/mL,P〈0.05]. CONCLUSIONS： Folic acid could prevent colorectal neoplasms in mice induced by DMH. The utilization of epigenetic target is an effective and valuable approach to chemotherapy as well as chemoprevention of cancer.

关 键 词：叶酸 DNA甲基化 肠肿瘤 基因 C-MYC 

分 类 号：R735.34[医药卫生—肿瘤]