Experimental Study Of Inhibitory Effect Of SiRNA Targeting Against Ang-2 In Human Pancreatic Carcinoma Mediated By Lentivirus In Vivo

PartⅠThe significance and correlation of Ang-2 expression in pancreatic carcinomaObjective To investigate the expressions of Angiopoietin-2 (Ang-2), and microvessel density(MVD) as well as the relationships among them,and the relationships to the clinicopathologic features of human pancreatic carcinoma.Methods The immunohistochemical SP method was used to determine the expression and distributing of Ang-2 and MVD in 30 cases of resected specimens of pancreatic carcinoma,compared with that normal pancreas tissues of 30 cases.The correlations among Ang-2 and MVD and their relationships to the clinicopathologic characteristics of human pancreatic carcinoma were analyzed.Results Higher expressions of Ang-2 and MVD were detected in pancreatic carcinoma than in normal pancreatic tissue,The percentage of Ang-2 protein positive expression was 56.7% in pancreatic carcinoma,while that was 14.3% in pancreatic tissue.There was statistical significance between the two groups.The average value of MVD was 35.4±3.2 in pancreatic carcinoma,while that was 14.2±2.9 in pancreatic tissue. There was statistical significance between the two groups.Conclusions Ang-2 is overexpressed in pancreatic carcinoma,and the value of MVD is higher than normal pancreatic tissue,the expression of Ang-2 is directly correlated with that the value of MVD significantly. Ang-2 may play an important role in the carcinogenesis and aggression in pancreatic carcinoma by promoting of pancreatic cancer angiogenesis. . PartⅡResearch for inhibition human pancreatic carcinoma by Ang-2-siRNA in vivoObjective To research inhibition of biological behaviors of human pancreatic carcinoma such as growth,metastasis and invasion by Ang-2-siRNA in vivo.Methods Human pancreatic carcinoma transplanted subcutaneously in nude mouse, divided them into experimental group, negative control group and blank control group randomly. LV-Ang-2-siRNA,LV-GFP and NS were intratumorally injected with 2×109TU respectively in subcutaneous xenograft model, Nude mice were sacrificed and tumor samples removed later, Ang-2 protein expressions as well as value of MVD were detected by immunohistochemical SP method, TUNEL staining and transmission electron microscopy were used to determine apoptosis and apoptosis index were measured.Results Growth rate of subcutaneous xenograft significantly decreased in experimental group , the tumor's size and weight of experimental group were significantly lesser than those of negative control group and blank control group (for volume, F=1508.6,P=0.0001; for weight, F=77.560,P=0.0001).For experimental group, expressions of Ang-2 proteins were weaker than those of control groups (F=29.148,P=0.0001), values of MVD and apoptotic index(AI) were significantly lesser than those of control groups (for MVD, F=7.185,P=0.005; for AI, F= 16.289,P=0.001).Conclusions LV-Ang-2-siRNA can dramatically inhibit the growth of human pancreatic carcinoma in vivo., promoting apoptosis through antiangiogenesis.