title: Impact of STAT3 inhibition on survival of osteosarcoma cell lines.
abstract: OBJECTIVE
  Osteosarcoma is often a fatal malignancy. Constitutive STAT3 activation is associated with various human cancers and commonly suggests poor prognosis. We aimed to investigate the effect and potential molecular mechanisms of STAT3 inhibition on osteosarcoma.
  
  
  METHODS
  STAT3 inhibitor S3I-201 was investigated in six osteosarcoma cell lines. Crystal violet colorimetric, clonogenic, cleaved caspase-3 assays and western blot were performed to measure the effect and mechanisms of STAT3 inhibition.
  
  
  RESULTS
  All osteosarcoma cell lines expressed phosphorylated STAT3. Anti-proliferative effects of S3I-201 were dose- and time-dependent. S3I-201 also inhibited colony-formation and induced apoptosis through the caspase cleavage pathway. Finally, molecular mechanism studies suggested that down-regulation of STAT3 phosphorylation and downstream STAT3-target genes such as cyclin D1 and survivin may contribute to S3I-201-mediated anti-proliferation and apoptosis.
  
  
  CONCLUSIONS
  Inhibition of STAT3 signalling suppressed osteosarcoma cell growth and induced apoptosis, and indicated that STAT3 targeted-therapy may have therapeutic potential in osteosarcoma.
authors.affiliation: Sarcoma Research Group, Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Randwick, Australia Department of Surgery, Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Randwick, Australia.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Randwick, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: Department of Surgery, Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Randwick, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Crowe
authors.affiliation: Sarcoma Research Group, Adult Cancer Program, Lowy Cancer Research Centre, Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Randwick, Australia Department of Surgery, Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, Randwick, Australia j.yang@unsw.edu.au.
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Yang
mesh_terms: D000636:Aminosalicylic Acids / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001557:Benzenesulfonates / Q000494:pharmacology*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
chemical_list: D000636:Aminosalicylic Acids; D001557:Benzenesulfonates; C520337:NSC 74859; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Osteosarcoma; S3I-201; STAT3