Chemotherapy and antiangiogenesis--drug-specific, dose-related effects.
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.
Lennernäs
Bo
B
Department of Oncology, Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Albertsson
Per
P
Lennernäs
Hans
H
Norrby
Klas
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000494:pharmacology; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D008643:Mesentery / Q000098:blood supply* / Q000187:drug effects; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015430:Weight Gain / Q000187:drug effects
D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate