Abstract
Paclitaxel (Taxol), a promoter of microtubule polymerization and a radiosensitizing agent, is one of the more active anticancer drugs in the current treatment of solid tumors. In this study, we show that paclitaxel possesses an antiangiogenic property associated with a down-regulation of vascular endothelial growth factor (VEGF) in a highly-vascularized transgenic murine breast cancer (Met-1). Paclitaxel, at non-cytotoxic doses of 0, 3 and 6 mg/kg/day, was administered intraperitoneally for 5 days to nude mice bearing the Met-1 breast tumor. Extent of intratumoral angiogenesis, as indicated by microvessel tortuosity and microvessel density, was significantly reduced by paclitaxel in a dose-dependent manner. Paclitaxel also suppressed expression of VEGF in the Met-1 cells transplanted in nude mice or maintained in cell culture. These results indicate that antiangiogenesis associated with a down-regulation of VEGF is an additional mode of action of paclitaxel.
MeSH terms
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Angiogenesis Inhibitors / administration & dosage
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Angiogenesis Inhibitors / therapeutic use*
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Animals
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Antineoplastic Agents, Phytogenic / administration & dosage
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Antineoplastic Agents, Phytogenic / therapeutic use*
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Endothelial Growth Factors / biosynthesis
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Endothelial Growth Factors / genetics
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Enzyme-Linked Immunosorbent Assay
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Injections, Intraperitoneal
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Lymphokines / biosynthesis
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Lymphokines / genetics
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Mammary Neoplasms, Experimental / blood supply
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Mammary Neoplasms, Experimental / drug therapy*
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Mice
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Mice, Nude
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Mice, Transgenic
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Microcirculation
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Paclitaxel / administration & dosage
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Paclitaxel / therapeutic use*
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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Angiogenesis Inhibitors
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Antineoplastic Agents, Phytogenic
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Endothelial Growth Factors
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Lymphokines
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Neoplasm Proteins
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Paclitaxel