| Summary: | 碩士 === 國立成功大學 === 微生物暨免疫學研究所 === 95 === Induction of angiogenesis plays an important role in the development and progression of most human tumors, including lung cancer. Currently available therapies for malignant lung cancer produce low response rates in patients. Therefore, more effective treatment modalities are needed. Therapeutic targeting of angiogenesis has recently been explored to inhibit malignant tumor growth and metastasis. In this study, the expression of human gene kallistatin in Lewis Lung carcinoma cells (LL/2), resulting in inhibiting the metastatic tumor growth and prolonging the survival of tumor bearing mice. Meanwhile, we constructed lentivirus vectors carrying human gene kallistatin (LV-Kallistatin) for gene therapy. By using the conditioned medium from LV-Kallistatin infected cells, we demonstrated that migration and proliferation of endothelial cell were inhibited. The similar results were also observed in migration, invasion and adhesion of LL/2. In experimental metastatic study, the wet lung weights from animals that received LV-Kallistatin were decreased compared with control-treated mice. Besides, the survival rate was dramatically extended in LV-Kallistatin treated group. By using the Enzyme-linked immunoassay (ELISA), we analyzed the cytokine expression at the tumor site. Tumor necrosis factor-α (TNF-α) was lower in LV-Kallistatin treated group compared with control group. On the contrary, transforming growth factor-β (TGF-β) was slightly higher in LV Kallistatin treated group than the control group. According to our findings, lentivirus mediated kallistatin expression has provided a promising therapeutic potential in cancer metastasis therapy.
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