中文摘要：

目的研究Dll-1／Notchl信号传导通路与结直肠癌病理学特征的关系，明确此通路对结直肠癌细胞增殖及凋亡的影响。方法应用固定化蛋白质印迹法检测63例结直肠癌组织及其邻近正常肠黏膜中Dll-1及Notchl蛋白表达；用Notchl通路中Jy-分泌酶抑制剂DAPT作用于结肠癌细胞系SW480，MTr法检测细胞增殖状态，流式细胞仪观察其对细胞凋亡的影响，固定化蛋白质印迹法检测Notchl胞内活性段及其靶基因产物Hes-1和Bcl-2蛋白的表达。分别采用独立样本t检验、配对样本t检验及单因素方差分析。结果结直肠癌组织中Notchl和Dll-1蛋白表达水平分别高于正常肠黏膜的1．75及2．21倍（t=2．554，P=0．012及t=3．565，P=0．005）；二者表达与肿瘤分化程度（t=2．463，P=0．017及t=2．390，P=0．019）、分期（t=2．675，P=0．007及t=2．310，P=0．021）及淋巴结转移（t=2．229，P=0．021及t：2．210，P=0．023）有关。用1-分泌酶抑制剂DAPT阻断Notchl通路可抑制SW480细胞的增殖，诱导其凋亡；同时NICD和Bcl-2的表达水平随作用时间延长而降低。结论Dll-1及Notchl的高表达与结直肠癌病理学特征密切相关，阻断Notchl通路可抑制Bcl-2表达，同时可抑制结肠癌细胞的增殖，并诱导其凋亡。

英文摘要：

Objective To study the relationship of Dll-1/Notch signal transduction pathway with the pathological characteristics of colorectal cancer and the effect on proliferation and apoptosis of colorectal cancer cells. Methods We assessed Notchl and Dll-1 protein levels in 63 cases of colorectal cancer and adjacent normal tissue by Western blotting. SW480 cells were treated with DAPT （γ-secretase inhibitor） at different treating times. MTT assay and flow cytometry were used to measure the proliferation and apoptosis of SW480 cells, seperately. The expression of the intracellular domain of Notch （ NICD）, Hes-1 and Bclo2 were measured by Western blotting. Statistical methods were used including independent samples t test, paired sample t test and single factor analysis of variance. Results Notchl and Dll-1 protein level increased in colorectal cancer tissues compared with adjacent normal mucosa, the mean values were 1.75- fold and 2. 21-fold, respectively（ t = 2. 554 ,P = 0. 012 and t = 3. 565, P = 0. 005 ）. Also we found that the overexpression of Notchl and Dll-1 was related to the differentiation（ t = 2. 463 ,P = 0. 017 and t = 2. 390, P=0.019）, staging（t =2.675,P =0.007 and t =2.310,P =0.021） and lymph nodes metastasis（t = 2. 229,P =0. 021 and t =2. 210,P =0. 023） of colorectal cancer. Treating SW480 cell with Notch pathway inhibitor （~-secretase inhibitor, DAPT） resulted in growth inhibition, apoptosis induction and there was downregnlation of NICD and Bcl-2 expression along with the treating time. Conclusions Overexpression of Notchl and Dll-1 is related to the pathological characteristics of colorectal cancer. Blockade of Notchl signal pathway may inhibit cell proliferation and induce cell apoptosis of coloreetal cancer, as well as inhibit the expression of Bcl-2.