RRC ID 42243
Author Minagawa N, Nakayama Y, Inoue Y, Onitsuka K, Katsuki T, Tsurudome Y, Shibao K, Hirata K, Sako T, Nagata N, Ohie S, Kohno K, Itoh H.
Title 4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid inhibits angiogenesis in colon cancer through reduced expression of vascular endothelial growth factor.
Journal Oncol. Res.
Abstract 4-[3,5-bis(trimethylsilyl)benzamido] Benzoic acid (TAC-101) has potent antiproliferative, antiangiogenic, and antitumor effects in vitro and in vivo. These effects might be due to TAC-101 binding to retinoic acid receptor alpha (RAR-alpha) and interfering with the binding of activator protein-1 (AP-1) to DNA. However, little is known about the detailed mechanism of TAC-101 function. We investigated the mechanism of the antiangiogenic effect of TAC-101 using a rat hepatic metastatic model in vivo and DLD-1 human colon cancer cells in vitro. Liver metastases were induced by portal injection of RCN-9 rat colonic cancer cells into F344 rats. TAC-101 (8 mg/kg) was orally administered 5 days per week for 4 weeks and then hepatic tumors were immunohistochemically evaluated for microvessel density (MVD) and vascular endothelial growth factor (VEGF). TAC-101 significantly reduced both MVD and VEGF expression. Northern blot analysis and ELISA indicated that TAC-101 efficiently inhibited production of VEGF mRNA and protein in DLD-1 cells in a time- and dose-dependent manner. These findings suggest that TAC-101 may inhibit progression and metastasis in colon cancer by interfering with tumor production of VEGF.
Volume 14(9)
Pages 407-14
Published 2004
PMID 15490972
MeSH Angiogenesis Inhibitors / pharmacology Angiogenesis Inhibitors / therapeutic use* Animals Benzoates / pharmacology Benzoates / therapeutic use* Cell Line, Tumor Colonic Neoplasms / drug therapy* Colonic Neoplasms / metabolism Dose-Response Relationship, Drug Gene Expression Regulation, Neoplastic / drug effects* Gene Expression Regulation, Neoplastic / physiology Humans Liver Neoplasms, Experimental / drug therapy Liver Neoplasms, Experimental / metabolism Liver Neoplasms, Experimental / secondary Neovascularization, Pathologic / drug therapy Neovascularization, Pathologic / metabolism Rats Rats, Inbred F344 Trimethylsilyl Compounds / pharmacology Trimethylsilyl Compounds / therapeutic use* Vascular Endothelial Growth Factor A / antagonists & inhibitors* Vascular Endothelial Growth Factor A / biosynthesis Vascular Endothelial Growth Factor A / genetics
IF 3.143
Times Cited 13
Human and Animal Cells