title: Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis.
abstract: Increased vascular endothelial growth factor (VEGF) expression is associated with colon cancer metastases. We hypothesized that inhibition of VEGF receptor activity could inhibit colon cancer liver metastases. BALB/c mice underwent splenic injection with CT-26 colon cancer cells to generate metastases. Mice received daily i.p. injections of vehicle, tyrosine kinase inhibitor for Flk-1/KDR (SU5416) or tyrosine kinase inhibitor for VEGF, basic fibroblast growth factor, and platelet-derived growth factor receptors (SU6668). SU5416 and SU6668 respectively inhibited metastases (48.1% and 55.3%), microvessel formation (42.0% and 36.2%), and cell proliferation (24.4% and 27.3%) and increased tumor cell (by 2.6- and 4.3-fold) and endothelial cell (by 18.6- and 81.4-fold) apoptosis (P<0.001). VEGF receptor inhibitors increased endothelial cell apoptosis, suggesting that VEGF may serve as an endothelial survival factor.
authors.affiliation: Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Shaheen
authors.forename: D W
authors.initials: DW
authors.lastname: Davis
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: B K
authors.initials: BK
authors.lastname: Zebrowski
authors.forename: M R
authors.initials: MR
authors.lastname: Wilson
authors.forename: C D
authors.initials: CD
authors.lastname: Bucana
authors.forename: D J
authors.initials: DJ
authors.lastname: McConkey
authors.forename: G
authors.initials: G
authors.lastname: McMahon
authors.forename: L M
authors.initials: LM
authors.lastname: Ellis
mesh_terms: D000818:Animals; D017209:Apoptosis; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004727:Endothelium / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D020287:In Situ Nick-End Labeling; D007211:Indoles / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011758:Pyrroles / Q000494:pharmacology*; D011897:Random Allocation; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects*; D017978:Receptors, Growth Factor / Q000187:drug effects*; D040262:Receptors, Vascular Endothelial Growth Factor; D014407:Tumor Cells, Cultured
chemical_list: D007211:Indoles; D011758:Pyrroles; D017978:Receptors, Growth Factor; C116890:Semaxinib; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor