Antitumor Effects of Synthetic VEGF-receptor Binding Antagonist, VGA1155

Vascular endothelial growth factor (VEGF) plays key roles in tumor angiogenesis. Therefore, VEGF and its receptors are considered to be primary targets for anti- angiogenic strategy during cancer chemotherapy. Our previous study reported that VGA1155, a low-molecular-weight inhibitor of the binding of VEGF, inhibited VEGF binding to KDR/Flk-1 receptor-overexpressing cells. In the present study, the antitumor effects and antimetastatic effect of VGA1155 were examined in vivo. VGA1155 suppressed the growth of human lung, breast, colon and epidermoid cancers (LC-6, HT29, MX-1, Col-1 and A431) in the nude mouse xenograft model, and pulmonary metastasis of melanoma in the spontaneous metastasis model. These results suggest that VGA1155 has antitumor effects in vivo through the inhibition of VEGF binding to its receptors. Tumor angiogenesis, the generation of new blood vessels in response to angiogenic stimuli from tumor cells, promotes solid tumor progression by stimulating tumor cell survival, tumor invasion and metastasis (1). The growth of solid tumors is dependent on angiogenesis, as tumors generally cannot grow beyond the size of 1-2 mm in diameter without the formation of new blood vessels to supply nutrition and oxygen. Among a large number of pro-angiogenic factors, vascular endothelial growth factor (VEGF) and VEGFR2