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 antiangiogenic 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.
Ueda
Yasuji
Y
Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan. y.ueda@po.rd.taisho.co.jp
Yamagishi
Takehiro
T
Samata
Kazunori
K
Hirayama
Noriko
N
Aozuka
Yasushi
Y
Tanaka
Makoto
M
Nakaike
Shiro
S
Saiki
Ikuo
I
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001565:Benzoates; C487956:VGA1155; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor