title: Role of peroxisome proliferator activated receptor-gamma in bacillus Calmette-Guérin bladder cancer therapy.
abstract: OBJECTIVE
  We evaluated the effects of combined PPARg agonist with bacillus Calmette-Guérin in bladder cancer growth in vitro and in vivo, focusing on the tissue remodeling mechanisms induced by bacillus Calmette-Guérin.
  
  
  METHODS
  PPARs are a superfamily of nuclear receptors that are transcription factors activated by ligands. Activation of PPARg, the γ subtype, causes proliferation inhibition or differentiation of tumor cells. Previously, we reported that the inhibition of murine bladder tumor growth induced by bacillus Calmette-Guérin, which is the standard treatment for patients with nonmuscle invasive, high grade bladder cancer, increased PPARg expression in vitro and in vivo. In vitro the cell growth inhibition induced by bacillus Calmette-Guérin was enhanced by the PPARg agonist 15-d-PGJ2, raising the possibility that PPARg activation may be a therapeutic modality for this disease.
  
  
  RESULTS
  In MB49 cells bacillus Calmette-Guérin and 15-d-PGJ2 induced PPARg expression, nuclear translocation and transcriptional activity. In vivo bacillus Calmette-Guérin reduced tumor size, an effect that was partially reversed when bacillus Calmette-Guérin was combined with the PPARg agonist rosiglitazone. The same result was found when we analyzed the effect of the PPARg antagonist BADGE (Fluka Chemical, Buchs, Switzerland) combined with bacillus Calmette-Guérin. Analysis of the activation of macrophages and fibroblasts demonstrated that rosiglitazone inhibited the tissue remodeling mechanisms induced by bacillus Calmette-Guérin.
  
  
  CONCLUSIONS
  Results suggest that PPARg is involved in the antitumor action of bacillus Calmette-Guérin. However, exogenous PPARg agonists would not be a favorable therapeutic modality because they can inhibit the tissue remodeling needed for an overall satisfactory bacillus Calmette-Guérin response.
authors.affiliation: Área Investigación, Instituto de Oncología Ángel H Roffo, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Yanina
authors.initials: Y
authors.lastname: Langle
authors.forename: Catalina
authors.initials: C
authors.lastname: Lodillinsky
authors.forename: Denise
authors.initials: D
authors.lastname: Belgorosky
authors.forename: Eduardo Omar
authors.initials: EO
authors.lastname: Sandes
authors.forename: Ana María
authors.initials: AM
authors.lastname: Eiján
mesh_terms: D000283:Administration, Intravesical; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D009163:Mycobacterium bovis; D047495:PPAR gamma / Q000187:drug effects* / Q000235:genetics; D020675:Peroxisomes / Q000187:drug effects*; D012016:Reference Values; D000077154:Rosiglitazone; D012680:Sensitivity and Specificity; D045162:Thiazolidinediones / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone