Paclitaxel (Taxol): an inhibitor of angiogenesis in a highly vascularized transgenic breast cancer.
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.
Lau
D H
DH
Department of Internal Medicine, School of Medicine, University of California, Davis, Sacramento 95817, USA. derick.lau@ucdmc.ucdavis.edu
Xue
L
L
Young
L J
LJ
Burke
P A
PA
Cheung
A T
AT
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008222:Lymphokines / Q000096:biosynthesis / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D008833:Microcirculation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D017239:Paclitaxel