title: Determinants for in vivo antitumor effect of angiogenesis inhibitor SU5416 formulated in PEGylated emulsion.
abstract: Angiogenesis, the sprouting of capillaries from preexisting ones, is essential for the sustained growth of solid tumors. In this study, we used SU5416, a hydrophobic molecule with potent tyrosine kinase inhibitor of type 2 receptor for vascular endothelial growth factor (VEGF), as PEGylated emulsion (SU5416-PE), and evaluated the antitumor potency of this formulation in Lewis lung cancer (LLC), Colon-26 (C26), and B16BL6 melanoma (B16) tumor-bearing mice. Intravenous injection of SU5416-PE into tumor-bearing mice significantly suppressed the growth of C26 and B16 tumors, but had no effect on the growth of LLC tumors. MTT assay revealed that SU5416 inhibited the proliferation of human umbilical vein endothelial cells in a concentration-dependent manner but did not show such an inhibitory effect on all types of tumor cells examined, demonstrating the specificity of SU5416 for endothelial cells. Considering that VEGF levels within C26 and B16 tumors were found to be about 10-fold and 20-fold higher than that in LLC tumors, respectively, it was suggested that SU5416-PE would inhibit angiogenesis in certain types of tumor tissue such as C26 and B16 where VEGF plays a major role for promoting angiogenesis, leading to the suppression of in vivo tumor growth.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, 700-8530, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Ogawara
authors.forename: Shigeki
authors.initials: S
authors.lastname: Abe
authors.forename: Keita
authors.initials: K
authors.lastname: Un
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yoshizawa
authors.forename: Toshikiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Higaki
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D004655:Emulsions / Q000737:chemistry*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D011758:Pyrroles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004655:Emulsions; D007211:Indoles; D014677:Pharmaceutical Vehicles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols; C116890:Semaxinib
keywords: angiogenesis; cancer; drug delivery; emulsion; endothelial; solubility; vascular endothelial growth factor