title: COX-2 inhibitor celecoxib suppresses tumor growth and lung metastasis of a murine mammary cancer.
abstract: BACKGROUND
  The antitumor growth and antimetastatic actions of celecoxib [a selective cyclooxygenase-2 (COX-2) inhibitor] were investigated in a metastatic murine mammary cancer model.
  
  
  METHODS
  Mice bearing mammary tumors, developed after inoculation of syngeneic BALBIc mice with a mammary carcinoma cell line carrying a p53 mutation, were treated with celecoxib at 0, 7.5 and 15 mg/kg five times a week for seven weeks.
  
  
  RESULTS
  Tumor volumes were significantly reduced in association with an increase in apoptosis and a decrease in DNA synthesis in tumor tissues. In vitro studies demonstrated a significant increase in the number of cells undergoing apoptosis, with significantly elevated activities of caspase-3 and caspase-9, but not caspase-8, and a dose-dependent decrease in mitochondrial membrane potential, indicating the mitochondrial pathway of apoptosis. In addition, treatment with celecoxib showed cell cycle arrest in the G -phase and decreased cell population in the S- and G2/M-phases. Furthermore, tumor microvessel formation and mRNA levels for VEGF-A and COX-2 were markedly decreased.
  
  
  CONCLUSIONS
  Celecoxib may be useful as an adjuvant therapy for breast cancer containing p53 mutations due to its ability to both induce p53-independent mitochondria-mediated apoptosis and exert anti-angiogenic potential.
authors.affiliation: Department of Anatomy and Cell Biology, Division of Basic Medicine I, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yoshinaka
authors.forename: Masa-Aki
authors.initials: MA
authors.lastname: Shibata
authors.forename: Junji
authors.initials: J
authors.lastname: Morimoto
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Tanigawa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Otsuki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D000068579:Celecoxib; D002455:Cell Division / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib