title: The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of secondary bone tumors: an intravital microscopy study in mice.
abstract: BACKGROUND
  The inhibition of angiogenesis is a promising strategy for the treatment of malignant primary and secondary tumors in addition to established therapies such as surgery, chemotherapy, and radiation. There is strong experimental evidence in primary tumors that Cyclooxygenase-2 (Cox-2) inhibition is a potent mechanism to reduce angiogenesis. For bone metastases which occur in up to 85% of the most frequent malignant primary tumors, the effects of Cox-2 inhibition on angiogenesis and tumor growth remain still unclear. Therefore, the aim of this study was to investigate the effects of Celecoxib, a selective Cox-2 inhibitor, on angiogenesis, microcirculation and growth of secondary bone tumors.
  
  
  METHODS
  In 10 male severe combined immunodeficient (SCID) mice, pieces of A549 lung carcinomas were implanted into a newly developed cranial window preparation where the calvaria serves as the site for orthotopic implantation of the tumors. From day 8 after tumor implantation, five animals (Celecoxib) were treated daily with Celecoxib (30 mg/kg body weight, s.c.), and five animals (Control) with the equivalent amount of the CMC-based vehicle. Angiogenesis, microcirculation, and growth of A549 tumors were analyzed by means of intravital microscopy. Apoptosis was quantified using the TUNEL assay.
  
  
  RESULTS
  Treatment with Celecoxib reduced both microvessel density and tumor growth. TUNEL reaction showed an increase in apoptotic cell death of tumor cells after treatment with Celecoxib as compared to Controls.
  
  
  CONCLUSIONS
  Celecoxib is a potent inhibitor of tumor growth of secondary bone tumors in vivo which can be explained by its anti-angiogenic and pro-apoptotic effects. The results indicate that a combination of established therapy regimes with Cox-2 inhibition represents a possible application for the treatment of bone metastases.
authors.affiliation: Department of Orthopedic Surgery, Inselspital, University of Bern, CH-3010 Bern, Switzerland. frank.klenke@dkf.unibe.ch
authors.forename: Frank Michael
authors.initials: FM
authors.lastname: Klenke
authors.forename: Martha-Maria
authors.initials: MM
authors.lastname: Gebhard
authors.forename: Volker
authors.initials: V
authors.lastname: Ewerbeck
authors.forename: Amir
authors.initials: A
authors.lastname: Abdollahi
authors.forename: Peter E
authors.initials: PE
authors.lastname: Huber
authors.forename: Axel
authors.initials: A
authors.lastname: Sckell
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000556:secondary; D000068579:Celecoxib; D045744:Cell Line, Tumor; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D018715:Microscopy, Video; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib