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.
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Authors | Noritaka Minagawa, Yoshifumi Nakayama, Yuzuru Inoue, Koji Onitsuka, Takefumi Katsuki, Yosuke Tsurudome, Kazunori Shibao, Keiji Hirata, Tatsuhiko Sako, Naoki Nagata, Shinji Ohie, Kimitoshi Kohno, Hideaki Itoh |
Journal | Oncology research
(Oncol Res)
Vol. 14
Issue 9
Pg. 407-14
( 2004)
ISSN: 0965-0407 [Print] United States |
PMID | 15490972
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Benzoates
- TAC 101
- Trimethylsilyl Compounds
- Vascular Endothelial Growth Factor A
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Topics |
- Angiogenesis Inhibitors
(pharmacology, therapeutic use)
- Animals
- Benzoates
(pharmacology, therapeutic use)
- Cell Line, Tumor
- Colonic Neoplasms
(drug therapy, metabolism)
- Dose-Response Relationship, Drug
- Gene Expression Regulation, Neoplastic
(drug effects, physiology)
- Humans
- Liver Neoplasms, Experimental
(drug therapy, metabolism, secondary)
- Neovascularization, Pathologic
(drug therapy, metabolism)
- Rats
- Rats, Inbred F344
- Trimethylsilyl Compounds
(pharmacology, therapeutic use)
- Vascular Endothelial Growth Factor A
(antagonists & inhibitors, biosynthesis, genetics)
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