The Inhibition Of Lewis Lung Carcinoma In Mice By Adenovirus Vector Mediated Angiostatin

The malignant tumor has become a large sort of disease that is a serious hazard to human health. Its morbidity and mortality increase year by year, but the traditional radiation therapy, chemotherapy treatment and surgery have some shortcomings. These therapies can obtain the satisfactory curative effect in the early phase, but for the patients with the local proliferation and distant metastasis, these therapies do not significantly prolong the survival time of patients and improve life quality of patients, therefore, there is an urgent need to find new treatment methods.Both of tumor growth and metastasis depend on vasculanization, and the angiogenesis not only provide nutrition for the tumor growth but also the possible of tumor proliferation and metastasis. In China, lung carcinoma seriously threatens the health of people, and the formation of neovascularization has a direct relation with the degree of malignancy of lung carcinoma and prognosis, so that the anti-tumor angiogenesis of lung carcinoma treatment in recent years has become a hot spot. Angiostatin, as inhibitory factor of tumor angiogenesis: in vitro can inhibit the proliferation and migration of the normal vascular endothelial cell, induce endothelial cell apoptosis and reduce the invasion of endothelial cells and the formation of blood vessel, however, in vivo it is confirmed that it can inhibit the growth of primary tumors and metastatic tumor by the experiment. We use adenovirus vector carrying angiostatin gene to investigate the inhibition effect to Lewis lung carcinoma in mice, to provide theoretical and experimental basis for anti-angiogenesis gene therapy in clinic treatment.Experimental groups were divided in model group, AdCMV-angiostatin group, prevent group and AdCMV-LacZ group. By measuring tumor size, growth curve, combined with pathological changes in tumor tissue, and calculated the microvessel density, apoptotic index and proliferation index in each group, using of RT-PCR and Western Blotting methods, to investigate expression of angiostatin in mRNA and protein levels among the model group, AdCMV-LacZ group, AdCMV-angiostatin group and prevent group.The results prove that AdCMV-angiostatin can inhibit the growth of Lewis lung carcinoma in mice. The difference is significant compared the gross tumor volume of the model group with the gross tumor volume of the AdCMV-angiostatin group. Compared with the model group and the AdCMV-LacZ group, the mice tumor growth velocity in the prevent group and the AdCMV-angiostatin group is significantly slower. Compareing the model group and the AdCMV-LacZ group with the prevent group and the AdCMV-angiostatin group, the prevent group and AdCMV-angiostatin group's microvessel density decreased significantly, the apoptotic index incressed, the proliferation index decreased, and there are significant differences. Compared with the model group and AdCMV-LacZ group, in the prevent group and AdCMV-angiostatin group the expression of angiostatin in mRNA levels increased significantly. And Western Blotting prove that the expression of angiostatin in protein levels also increased in prevent group and AdCMV-angiostatin group.Conclusion: AdCMV-angiostatin can inhibit the growth of Lewis lung carcinoma in mice, degrade the tumorous angiogenesis and promote the tumor cells'apoptosis.