Colon cancer therapy targeting specific charactetistics of tumor vessel.

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Since it have been reported that angiogenesis plays an important role in cancer growth, various studies and therapies for tumor angiogenesis have been done. If specific charactetistics of tumor vessel find out, more effective atiangiogenic therapies may be put into practice. The tumor vessel is large and small, twisting, winding and leacky compared with normal vessel. This alterations may be caused by too much proliferative activity or unbalance of angiogenic factors in cancer tissues. We focus on Angiopoietin2/Angiopoietin1 balance, Alteration of this balance in experimental cancerous angiogenesis were examined with antiangiogenic effect of argatroban (new anticoagulant). Macroscopical Vascular structure, Count of vascular area, CD34microvessel density, angiogenic factor (Ang1,Ang2,VEGF) were measured in dorsal air sac model using S-180 sarcoma cell and COLO320DM colon cancer cell. Tube formation of HUVEC cells were tested by Matrigel. For adiministration of argatroban, tumor angiogenesis was statistically inhibited. Because Argatroban did not inhibited tube formation of HUVEC in martigel assey, this effect may not be direct action for endotherial cells. In this experiment model, the Ang2 to Ang1 ratio was always elevated during tumor angiogenesis, this phenomenon might caused abnormal tumor vasclular artitecture. These results suggest that Argatroban may have antitumor effect by inhibition of tumor angiogenesis. In addition, Rivision of Ang2/Ang1 ratio may related to antiangiogenic effect in cancer tissues.Focus on abnormal Nitric oxide synthesis of tumor vessel, Another experiment was done. In the same dorsal air sac model, N^G-nitro-L-arginine-methyl-ester (L-NAME), a NO synthase inhibitor was tested its anti-angiogenic effect with relationship between angiogenic growth factors. Administration of L-NAME significantly inhibited tumor angiogenesis. VEGF expression and mRNA levels in tissue surrounding tumor cells were significantly decreased.