title: Bortezomib inhibits angiogenesis and reduces tumor burden in a murine model of neuroblastoma.
abstract: BACKGROUND
  Bortezomib is a proteasome inhibitor with pleiotropic antitumor activity. Here we investigate the antiangiogenic and antitumor efficacy of bortezomib against neuroblastoma both in vitro and in a murine model of localized and disseminated disease.
  
  
  METHODS
  In vitro activity of bortezomib was assessed by evaluating its effect on cell proliferation and cell cycle status. Localized tumor burden was followed with caliper measurements and total-body bioluminescence in mice with disseminated disease. The antiangiogenic activity was evaluated with immunohistochemistry and human vascular endothelial growth factor (VEGF) enzyme-linked immunosorbent assay on tumor protein extracts.
  
  
  RESULTS
  Bortezomib treatment resulted in dose and time-dependent decreases in cell proliferation and resulted in cell cycle arrest. In vivo, bortezomib restricted tumor growth in a model of localized disease and decreased bioluminescence in mice with disseminated disease. That decreased bioluminescence reflected decreased tumor burden was confirmed at necropsy by assessing disease in specific organs. In addition, treatment resulted in a decrease in intratumoral vessel counts and reduced tumor VEGF expression.
  
  
  CONCLUSIONS
  Bortezomib shows significant activity against neuroblastoma in vitro, and it inhibits tumor growth and angiogenesis in vivo. These results suggest that clinical studies of bortezomib are warranted for the treatment of this difficult disease.
authors: Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tenn, USA.
authors: John B
authors: JB
authors: Hamner
authors: Paxton V
authors: PV
authors: Dickson
authors: Thomas L
authors: TL
authors: Sims
authors: Junfang
authors: J
authors: Zhou
authors: Yunyu
authors: Y
authors: Spence
authors: Cathy Y
authors: CY
authors: Ng
authors: Andrew M
authors: AM
authors: Davidoff
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D045744:Cell Line, Tumor; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D011719:Pyrazines / Q000494:pharmacology*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D040521:Subcutaneous Tissue; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib