| Objective: Pancreatic carcinoma is a kind of calamitous malignant tumor. The incidence rate was upgrading year by year and buildup 3～7 times in recent 30 years . The characteristic of pancreatic carcinoma which is abundant with blood supply and easy to metastasis and recurrence .The effectiveness of simple chems or radiotherapy isn't optismistic, and then the targeted therapy which to aim directly at inVasion may be eleaate the cure rate and improve prognosis of pancreatic carcinoma. Angiogenesis not only correlates with the growth and metastasis nsuggests of cacinoma but also has considerable eaaluated Value in pathologic grading of cancer ,healing and judgement of prognosis. With the progress of molecular biology and immunology, Vascularization and antiaascularization is gradully to become the emphasis of phymatology . The relationship of angiogenesis and cell adhesion molecule has become a focal point in recent years. It has been found that integrin aVβ3 not only has a high expression on the surface of the solid tumor cells but also has a strong expression in the endotheliocytes of the new blood Vessels in the tumor tissue.In this study, our aim is to explore the efficacy of antisense integrin aVβ3 in treating pancreatic carcinoma of mouse and the effect to angiogenesis and apoptosis.Methods: AlphaV/pcDNA3 and Beta3/pcDNA3 were transformed into competent E. coli cells and assayed after endonuclease cutting. 120 male mouse which were 4-6 weeks old were separated into 4 groups in random and each group had 30., the mixture of antisense integrin αV,β3 was injected and electrobloted into the tumor. Then we observe the growth of the tumors. After 6 weeks, we take the tumors, weight them and calculate the tumor inhibit rate. αV, β3 protein was examined by immunohistochemistry. Tumor micro αessel density (MVD) was assessed using the expression of factor VIII relatedantigen.TUNEL (TdT-mediated biotinylated-dUTP nick end labling method) was adopted to analysis apoptosis of tumor cells.Results: (1) The volumes of tumors were obviously different among each group. The tumor weight of each group was significantly different(P<0.01), and that of αV β3 group was lighter than those of αV, β3 group (P<0.05). The tumor inhibit rate of αV group, β3 group and αV β3 group was 5.832%, 6.711%, 20.421% respectively.(2) Protein of integrin αV and β3 expressed in all groups. In the control group, 12 cases were positive and the positive rate was 92.31. The positive rate of αV group,β3 group was 76. 92%, 80. 00% respectively and no difference was found among them(P>0.05), but significantly lower than that of the contrast group(P<0.01).(3)The MVD of the control group, αV group, β3 group and αV β3 group was 18.333 ± 1.398,13.800+1.063, 15.967 ± 1.245, 12.166±1.234. It was obviously that the MVD of αV group, β3 group and αV β3 group was evidently lower than the contrast group(P<0.01), but no difference was found among them(P>0.05).(4) The AI of the control group, αV group, β3 group and αVβ3 group was, 12.300 ± 1.393%, 22.167± 1.234%, 20.367 ± 1.066%, 24.100±0.995% respectively and had significant difference among them(P<0.01). The AI of αV β3 group was higher than that of αV group and β3 group (P<0.05), at the same time, the AI of β3 group was higher than that of αV group(P<0.05).Conclusions:(1) The antisense gene of integrin αV β3 can apparently inhibit the growth of tumor.(2) The antisense gene of integrin αV β3 may inhibit the angiogenesis of tumor.(3) The antisense gene of integrin αV β3 could accelerate apoptosis.(4) It is more efficient when the antisense gene of integrin αV with the antisense gene of integrin β3 are combinely used.
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