title: Effect of low-dose Paclitaxel and docetaxel on endothelial progenitor cells.
abstract: OBJECTIVE
  Bone marrow (BM)-derived endothelial progenitor cells (EPC) play an important role in neovascularization and tumor growth. It has been reported that docetaxel and paclitaxel inhibit angiogenesis, but the effect of docetaxel and paclitaxel on EPC-induced neovascularization has not been examined. We aimed to clarify the cytotoxic and inhibitory effects of these drugs on EPC.
  
  
  METHODS
  The effects of drugs on growth, tube formation, and migration of EPC were analyzed in vitro using a rat BM-derived EPC cell line (TR-BME). Fluorescence-labeled TR-BME cells were injected into tumor-bearing rats and accumulation at the tumor site was analyzed by fluorescence-activated cell sorting (FACS).
  
  
  RESULTS
  In in vitro cytotoxicity assays of these drugs in TR-BME, rat endothelial cell line TR-BBB and rat tumor cell line Walker 256, the IC(50) values for TR-BME were higher than those for TR-BBB or Walker 256. Both drugs inhibited tube formation and migration of TR-BME at lower concentrations than the cytotoxic IC(50). In vivo studies showed that a low dose of both drugs inhibited EPC accumulation at the tumor site in tumor-bearing rats, as determined by FACS, and caused a decrease in microvessel density.
  
  
  CONCLUSIONS
  Docetaxel and paclitaxel directly inhibited EPC-initiated vasculogenesis at low (non-cytotoxic) concentrations, causing suppression of tumor growth.
authors.affiliation: Department of Health and Dietetics, Faculty of Medical Health, Teikyo Heisei University, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Muta
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yanagawa
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Sai
authors.forename: Shigehira
authors.initials: S
authors.lastname: Saji
authors.forename: Eiji
authors.initials: E
authors.lastname: Suzuki
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Aruga
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Kuroi
authors.forename: Gaku
authors.initials: G
authors.lastname: Matsumoto
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.forename: Emi
authors.initials: E
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002279:Carcinoma 256, Walker / Q000188:drug therapy; D002460:Cell Line; D002464:Cell Migration Inhibition / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000187:drug effects*; D043823:Taxoids / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel