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Angiogenesis is a cooperative process that includes endothelial growth and sprouting and interaction with the surrounding matrix. The combined use of endothelial growth inhibitor and matrix blocker expected to inhibit the angiogenesis. Antiangiogenesis is one of strategies for treating cancer. Fumagillin is an inhibitor of type 2 methionine aminopeptidase and Cyclo (Arg-Gly-Asp-D-Phe-Val), an integrin ?v?3 antagonist can block blood vessel formation. In this study, male SCID mice were injected with colon cancer cells in the subcutis and then treated with Fumagillin and Cyclo. The tumor weight, microvessel density (MVD), and number of pulmonary metastatic foci were examined. Inhibitary effect of endothelial cell growth and tube formation was examined by human umbilical endothelial cells (HUVECs), which reflect the in vivo angiogenesis. The combination of Fumagillin and Cyclo-treated mice showed the greatest effect on the tumor mass reduction, lesser number of the pulmonary metastases, and lower MVD-CD105 levels than control animals. In vitro proliferation and tube formation of HUVEC was also decreased best by the combination of both. In conclusion, The combination of Fumagillin and Cyclo at their low doses, one tenth to one hundredth was found to suppress best colorectal cancer growth and metastasis by suppressing angiogenesis. |
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Keywords:Angiogenesis; Fumagillin; CYCLO |
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