title: Effects of brucine on vascular endothelial growth factor expression and microvessel density in a nude mouse model of bone metastasis due to breast cancer.
abstract: OBJECTIVE
  To study the effects of brucine on vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in a nude mouse model of bone metastasis due to breast cancer, and to assess the possible antitumor mechanism of brucine.
  
  
  METHODS
  A syringe needle was used to directly inject 0.2 mL monoplast suspension (with 2×10(5) human breast cancer cells contained) into the bony femoral cortex of the right hind leg for modeling. Twenty-five nude mice were randomized into five groups and administered with an intraperitoneal injection of saline or drug for 8 consecutive days: model group (0.2 mL normal saline), low-dose brucine group (1.73 mg·kg(-1)), medium-dose brucine group (3.45 mg·kg(-1)), high-dose brucine group (6.90 mg·kg(-1)), and thalidomide group (200 mg·kg(-1)). Diet and activity were recorded, and the tumors were harvested 5 weeks later. The percentage of VEGF-positive cells was determined with hematoxylin and eosin staining and immunohistochemical staining, and MVD expression was determined by optical microscopy.
  
  
  RESULTS
  The VEGF expressions in brucine- or thalidomide-treated mice were significantly reduced as compared with mice in the model group (P <0.01). There were no significant difference between the high-dose brucine group and the thalidomide group (P >0.05). Significant difference was between the high- and low-dose brucine group P<0.05). Further, VEGF expression was significantly increased in the low- and medium-dose brucine groups compared with the thalidomide group (P <0.05). The MVD values in the three brucine and thalidomide groups were significantly lower than that in the model group (P <0.01). The MVD values in the medium- and high-dose brucine groups were not significantly different from those in the thalidomide group (P >0.05), while the MVD value showed a significant increase in the low-dose group compared with the thalidomide group (P <0.05).
  
  
  CONCLUSIONS
  Brucine could inhibit the growth of breast cancer to bone metastases, possibly by inhibiting tumor angiogenesis.
authors.affiliation: Department of Traditional Chinese Medicine Oncology, Provincial Hospital of Anhui Medical University, Hefei 230001, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Ma
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Fu-Peng
authors.initials: FP
authors.lastname: Jin
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000556:secondary*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects / Q000473:pathology*; D013331:Strychnine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D042461:Vascular Endothelial Growth Factor A; C083806:brucine; D013331:Strychnine