A study on DH-1/Notch signal transduction pathway in colorectal cancer

Abstract

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 Bcl-2 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 Notch1 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 Notch1 and Dl1-1 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 (γ-secretase inhibitor,DAPT) resulted in growth inhibition,apoptosis induction and there was downregulation of NICD and Bcl-2 expression along with the treating time. Conclusions Overexpression of Notch1 and Dll-1 is related to the pathological characteristics of colorectal cancer.Blockade of Notch1 signal pathway may inhibit cell proliferation and induce cell apoptosis of colorectal cancer,as well as inhibit the expression of Bcl-2. Key words: Colorectal neoplasms; Adaptor proteins, signal transducing; Ligands; Receptor, Notch; Apoptosis