title: Pioglitazone inhibits growth of human retinoblastoma cells via regulation of NF-κB inflammation signals.
abstract: OBJECTIVE
  We aimed to study the antitumor effects of the PPARγ agonist pioglitazone on human retinoblastoma.
  
  
  METHODS
  The effects of pioglitazone on cell proliferation and apoptosis of the human retinoblastoma Y79 cells were investigated by MTT assay and Hoechst 33258 staining assay. The apoptosis related protein levels were detected by western blot. Inflammationary factors analysis was evaluated by western blot and ELISA. The effect of pioglitazone on nuclear factor-kappa B (NF-κB)-dependent reporter gene transcription induced by LPS was analyzed by NF-κB-luciferase assay. Then human retinoblastoma Y79 cells were subcutaneously transplanted in BALB/c nude mice and the animals were treated with pioglitazone to verify its antitumor effect in vivo.
  
  
  RESULTS
  Our data revealed that pioglitazone suppressed the viability of Y79 cells dose- and time-dependently and induced apoptosis in Y79 cells in vitro. Molecular biology analysis found that pioglitazone could affect the apoptosis and inflammation related signal via modulating the activity of NF-κB signal. Also we found that pioglitazone could markedly reduce the growth of Y79 cells transplanted into the mice without causing significant side effects.
  
  
  CONCLUSIONS
  Our results suggested that pioglitazone demonstrated antitumor activity against the human retinoblastoma Y79 cells by inhibiting cell growth, inducing apoptosis and modulating NF-κB pathway, and thus delayed tumor growth in vivo.
authors.affiliation: a Department of Ophthalmology , The First Affiliated Hospital, Henan University of Science and Technology , Luoyang , Henan , PR China.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Wang
authors.affiliation: b Department of Stomatology, Nanfang Hospital, Southern Medical University , Guangzhou , Guangdong Province , PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: c Department of Anatomy, Key Laboratory of Medical Biomechanics of Guangdong Province , Southern Medical University , Guangzhou , Guangdong Province , PR China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Bi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D000077205:Pioglitazone; D019572:Retinal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012175:Retinoblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D007004:Hypoglycemic Agents; D016328:NF-kappa B; D045162:Thiazolidinediones; D000077205:Pioglitazone
keywords: PPARγ; Pioglitazone; retinoblastoma; tumor growth