title: Celecoxib prevents tumor growth in an animal model by a COX-2 independent mechanism.
abstract: OBJECTIVE
  Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to reduce cell growth in several tumors. Among these possible antineoplastic drugs are cyclooxygenase- 2 (COX-2)-selective drugs, such as celecoxib, in which antitumoral mechanisms were evaluated in rats bearing Walker-256 (W256) tumor.
  
  
  METHODS
  W256 carcinosarcoma cells were inoculated subcutaneously (10(7) cells/rat) in rats submitted to treatment with celecoxib (25 mg kg(-1)) or vehicle for 14 days. Tumor growth, body-weight gain, and survival data were evaluated. The mechanisms, such as COX-2 expression and activity, oxidative stress, by means of enzymes and lipoperoxidation levels, and apoptosis mediators were also investigated.
  
  
  RESULTS
  A reduction in tumor growth and an increased weight gain were observed. Celecoxib provided a higher incidence of survival compared with the control group. Cellular effects are probably COX-2 independent, because neither enzyme expression nor its activity, measured by tumoral PGE(2), showed significant difference between groups. It is probable that this antitumor action is dependent on an apoptotic way, which has been evaluated by the expression of the antiapoptotic protein Bcl-xL, in addition to the cellular changes observed by electronic microscopy. Celecoxib has also a possible involvement with redox homeostasis, because its administration caused significant changes in the activity of oxidative enzymes, such as catalase and superoxide dismutase.
  
  
  CONCLUSIONS
  These results confirm the antitumor effects of celecoxib in W256 cancer model, contributing to elucidating its antitumoral mechanism and corroborating scientific literature about its effect on other types of cancer.
authors.affiliation: Department of Pharmacology, Federal University of Paraná, Biological Science Sector, Curitiba, Brazil.
authors.forename: Amanda Leite
authors.initials: AL
authors.lastname: Bastos-Pereira
authors.forename: Daiana
authors.initials: D
authors.lastname: Lugarini
authors.forename: Adriana de
authors.initials: Ad
authors.lastname: Oliveira-Christoff
authors.forename: Thiago Vinicius
authors.initials: TV
authors.lastname: Ávila
authors.forename: Simone
authors.initials: S
authors.lastname: Teixeira
authors.forename: Amanda do Rocio Andrade
authors.initials: Ado R
authors.lastname: Pires
authors.forename: Marcelo Nicolás
authors.initials: MN
authors.lastname: Muscará
authors.forename: Sílvia Maria Suter Correia
authors.initials: SM
authors.lastname: Cadena
authors.forename: Lucélia
authors.initials: L
authors.lastname: Donatti
authors.forename: Helena
authors.initials: H
authors.lastname: Cristina da Silva de Assis
authors.forename: Alexandra
authors.initials: A
authors.lastname: Acco
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D051020:bcl-X Protein / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; C494813:Bcl2l1 protein, rat; D052246:Cyclooxygenase 2 Inhibitors; D016166:Free Radical Scavengers; D011720:Pyrazoles; D013449:Sulfonamides; D051020:bcl-X Protein; D002374:Catalase; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D000068579:Celecoxib