論文 - 詳細
RRC ID | 42243 |
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著者 | 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. |
タイトル | 4-[3,5-Bis(trimethylsilyl)benzamido] benzoic acid inhibits angiogenesis in colon cancer through reduced expression of vascular endothelial growth factor. |
ジャーナル | 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. |
巻・号 | 14(9) |
ページ | 407-14 |
公開日 | 2004-1-1 |
DOI | 10.3727/0965040041791464 |
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 | 4.949 |
引用数 | 14 |
WOS 分野 | ONCOLOGY |
リソース情報 | |
ヒト・動物細胞 | CACO-2(RCB0988) PMF-ko14(RCB1426) |