Chemotherapy and antiangiogenesis: drug-specific effects on microvessel sprouting

• Tumors are angiogenesis dependent. Some chemotherapeutics have been shown to be able to suppress angiogenesis and thus tumor growth in vivo at low, well-tolerated doses. Not much is known about the angiogenesis-modulating effects of chemotherapeutics in vivo, however. Microvessel sprouting is inherent to angiogenesis. Using the rat mesentery assay, we studied the effect of cyclophosphamide, doxorubicin and paclitaxel at a low, atoxic dose on the number of sprouts per unit tissue volume (No. SP) and their length (Le. SP) at the edge of the expanding network in VEGF165-mediated angiogenesis. A single dose of each cytotoxic drug was administered i.v. 7 days before the animals were sacrificed. Cyclophosphamide significantly lengthened the shortest Le. SP and shortened the longest Le. SP, doxorubicin did not significantly affect Le. SP, whereas paclitaxel significantly shortened both the shortest and the longest Le. SP. No correlation was found between the present results and the distinctly drug-specific results of microvessel segment number and length analyzed within central parts of the same expanding network. To our knowledge, this is the first quantitative report on the effect of chemotherapy on angiogenesis sprouting in vivo. Collectively, the data suggest that cyclophosphamide, doxorubicin and paclitaxel at a non-toxic dose primarily target different intrinsic components of the angiogenic cascade, leading to distinctly drug-specific effects.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

Animals

Antibiotics

Antineoplastic/administration & dosage/*pharmacology

Antineoplastic Agents

Alkylating/administration & dosage/*pharmacology

Antineoplastic Agents

Phytogenic/administration & dosage/*pharmacology

Body Weight/drug effects

Cyclophosphamide/administration & dosage/*pharmacology

Doxorubicin/administration & dosage/*pharmacology

Endothelial Cells/drug effects

Injections

Intravenous

Male

Mesentery/anatomy & histology/drug effects

Microcirculation/anatomy & histology/drug effects

Neovascularization

Physiologic/*drug effects

Paclitaxel/administration & dosage/*pharmacology

Rats

Rats

Sprague-Dawley

Vascular Endothelial Growth Factor A

Publication and Content Type

ref (subject category)

art (subject category)