Abstract
Dose-response effects of fluorouracil, paclitaxel, doxorubicin, cisplatin, methotrexate, cyclophosphamide and etoposide on VEGF165/164-mediated angiogenesis using the rat mesenteric-window angiogenesis assay are reported. VEGF is a pivotal pro-angiogenic factor in most tumors. Microvessel spatial extension, density, pattern formation and segment length were assessed quantitatively and objectively. A single i.v. injection of each drug was given at a low, intermediate or high dose, 7 days before sacrifice. All the drugs elicited significant responses in terms of one or more measured variables. Only paclitaxel, doxorubicin and cyclophosphamide significantly suppressed the overall angiogenic response (p < or = 0.0001, p < or = 0.0002 and p < or = 0.05, respectively), however. Taking toxicity into account, paclitaxel was more potent in inhibition of angiogenesis than the other agents. No clear correlation was found between drug half-life, the degree of toxic effects (in terms ofbody weight changes) and the antiangiogenic effect. The antiangiogenic effects were distinctly drug specific.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / pharmacology*
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Cisplatin / administration & dosage
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Cisplatin / pharmacology
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Cyclophosphamide / administration & dosage
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Cyclophosphamide / pharmacology
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Dose-Response Relationship, Drug
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Doxorubicin / administration & dosage
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Doxorubicin / pharmacology
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Endothelial Growth Factors / pharmacology
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Etoposide / administration & dosage
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Etoposide / pharmacology
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Fluorouracil / administration & dosage
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Fluorouracil / pharmacology
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Humans
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Injections, Intravenous
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Intercellular Signaling Peptides and Proteins / pharmacology
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Lymphokines / pharmacology
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Male
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Mesentery / blood supply*
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Mesentery / drug effects
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Methotrexate / administration & dosage
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Methotrexate / pharmacology
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Neovascularization, Physiologic / drug effects*
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Paclitaxel / administration & dosage
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Paclitaxel / pharmacology
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Rats
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Rats, Sprague-Dawley
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Weight Gain / drug effects
Substances
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Antineoplastic Agents
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Endothelial Growth Factors
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Intercellular Signaling Peptides and Proteins
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Lymphokines
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Etoposide
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Doxorubicin
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Cyclophosphamide
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Paclitaxel
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Cisplatin
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Fluorouracil
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Methotrexate