| Objective : Colorectal carcinoma is one of the digestive system carcinoma which threat the health of human seriously, statistic reports shows that its rank in 3rd in common carcinoma, the morbidity and fatality are raised day by day. Colorectal carcinoma is a result of the interaction between multi-factors and multi-genes. Notch-1 consist of extracellular domain which comprised by a variety of epidermal growth factor repeats and intracellular domain comprised by different structures, relative molecular mass is 30 k D, C-terminal located in cytoplasm and N-terminal outside the cell membrane. It is a highly conserved molecular that exist in biological evolution widely, and participate in cell signal transmission, regulate proliferation, differentiation and apoptosis, and have a close relationship with tumorigenesis. We found that Notch-1 was overexpression in colorectal carcinoma, and had a relationship with tumorigenesis of colorectal carcinoma. In the work, we examined the expression of Notch-1 in tissues by q RT-PCR, and study the influence of different concentration of DAPT to proliferation activity and apoptosis of cancer cells, provide a theoretical foundation for understanding the role of Notch-1 take part in the pathogenesis of colorectal carcinoma.Methods:1 40 cases fresh specimens were collected, included carcinoma tissues and normal mucous tissues. All the specimens were come from the First Hospital of Hebei Medical University and Fourth Hospital of Hebei Medical University between September, 2002 and September 2012. All the patients were not received chemotherapy and radiotherapy before operation.2 HCT116 was selected for cell culture.3 The expression of Notch-1 in 40 cases cancer tissues and correspond normal tissues were detected by q RT-PCR, and analyzed the relationship between the expression of Notch-1 and clinicopathologic feature.4 Cells that treated by different concentration of DAPT served as experimental group, and untreated cells as control group.5 OD values were detected by CCK-8 at different times after the treatment was performed, to observe the proliferation difference between control group and experimental group.6 Flow cytometry was performed in control group and experimental group to compare the difference.7 All the results were analyzed by SPSS19.0 and Graph Pad Prism 5.0, the results were showed by median(quartile), Wilcoxon test was used to analyzed paired samples, One-way ANOVA was used to analyzed multiple groups comparison, Two-way ANOVA was used to analyzed repeated measure data. Kaplan-Meier survival curve was drawn. Survival time was between the operation day and the last follow up, calculated on month. Multi-factor survival analysis was performed by Cox regression analysis. P<0.05 was regarded as statistical significance.Results:1 The expression of Notch-1 in colorectal cancer tissues and normal tissues were 0.0568(0.0302,0.0757) and 0.0107(0.0068,0.0231), respectively. The expression of Notch-1 in cancer tissues was higher than in normal tissues(P<0.0001), the difference was statistically significance.2 The expression of Notch-1 in large tumor group(equal or greater than 5cm) were higher than small group(less than 5cm), the difference was statistically significance(P=0.0236). Notch-1 was independent with lymph nodes metastasis, age, gender, depth of invasion.3 DAPT could down-regulate the expression of Notch-1.4 Cell proliferation was detected by CCK-8 after the treatment of DAPT. The results shown that 10μM DAPT could suppress the cell propagation obviously, the difference was statistically significance(P<0.0001).5 Compared with control group( 0.2950±0.1530) %, 10μM DAPT promoted the early apoptosis rate obviously(2.785±0.4070), the difference was statistically significance(P=0.0046). 5μM and 1μM DAPT could also promote the apoptosis rate, but the difference has no statistically significance.6 Survival rate analysis shown that the survival rate of patients was correlated with lymph nodes metastasis(P=0.0002)and depth of invasion(P=0.0137), the difference was statistically significance.7 Cox multiple factor survival analysis shown that the lymph nodes metastasis was the independent risk factor that impacted the survival rate of colorectal carcinoma patients(P=0.003). The gender, age, tumor volume, Notch-1 level and depth of invasion were no relevance with patient survival rate.Conclusions:1 The expression of Notch-1 is high level in colorectal carcinoma, suggesting that Notch-1 may probably have a potential oncogene activity.2 The expression of Notch-1 is up-regulated even more in the tumor which is equal or greater than 5cm, suggesting that it has significance in judging grade malignancy and prognosis of colorectal carcinoma.3 Notch-1 may play an oncogene activity by promoting the proliferation of cancer cells.4 The survival rate of colorectal carcinoma patients was related to lymph nodes metastasis and tumor invasion depth. |
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