title: Metronomic docetaxel chemotherapy inhibits angiogenesis and tumor growth in a gastric cancer model.
abstract: OBJECTIVE
  Low-dose metronomic (LDM) chemotherapy represents a new strategy to treat solid tumors by stronger antiangiogenic activity and less side effects. The aim of the study is to rationally develop a docetaxel metronomic regimen in preclinical settings of gastric cancer.
  
  
  METHODS
  In vitro cell proliferation, apoptosis, and thrombospondin-1/vascular endothelial growth factor (TSP-1/VEGF) expression analyses were performed on human umbilical vein endothelial cells (HUVECs) and gastric cancer (BGC-823) cells exposed for 144 h to metronomic concentrations of docetaxel. BGC-823 human gastric cancer xenograft model was used, and tumor growth and side effects were closely monitored. Quantitative real-time PCR was used to determine TSP-1/VEGF mRNA levels in tumor samples. Expression of VEGF and CD31 was observed by immunohistochemistry.
  
  
  RESULTS
  Our results indicated that LDM docetaxel preferentially inhibited HUVEC cell proliferation and induced HUVEC apoptosis. Docetaxel significantly increased TSP-1 expression and secretion in HUVEC cells whereas the expression and secretion of VEGF significantly decreased in BGC-823 cells. LDM docetaxel significantly inhibited BGC-823 tumor growth in the absence of toxicity, which was accompanied by decreases in microvessel density (MVD) and VEGF and increases in TSP-1 gene expression in tumor tissues.
  
  
  CONCLUSIONS
  In vitro results show the antiangiogenic properties of LDM docetaxel. In vivo, LDM docetaxel treatment is effective against gastric tumor and microvessel growth without toxic effect on nude mice.
authors.affiliation: Fourth Laboratory of Cancer Institute, Department of Tumor Pathology of General Surgery Institute, No.1 Hospital of China Medical University, 155 Nanjing North Street, 110001, Heping District, Shenyang, Liaoning Province, China.
authors.forename: Hongju
authors.initials: H
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Xin
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Sun
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.forename: Yueyun
authors.initials: Y
authors.lastname: Hu
authors.forename: Shasha
authors.initials: S
authors.lastname: Wang
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D014471:Umbilical Veins / Q000166:cytology; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel