title: Hedgehog signal inhibitor forskolin suppresses cell proliferation and tumor growth of human rhabdomyosarcoma xenograft.
abstract: OBJECTIVE
  We have previously reported that the Hedgehog (Hh) signaling pathway is activated in pediatric malignancies. In this study, we examined the effect of the Hh signal inhibitor forskolin on the growth of rhabdomyosarcoma (RMS) in vivo and in vitro and thereby elucidated the possibility of considering Hh signaling pathway as a therapeutic target for RMS.
  
  
  METHODS
  We evaluated the messenger RNA expressions of Hh signal mediators in 3 human RMS cell lines using reverse transcriptase-polymerase chain reaction method. The effect of forskolin on the tumor cell proliferation was investigated using WST-1 assay (Dojindo Co, Kumamoto, Japan). We inoculated 10(7) tumor cells into the back of nude mice to create RMS xenograft tumor models. Forskolin was subcutaneously administered in the region around the tumor, and the effect on the tumor growth was evaluated.
  
  
  RESULTS
  The messenger RNA expression of glioma-associated oncogene homolog 1, the marker of Hh signaling activation, was expressed at various levels in RMS cell lines. The proliferation of RMS cells was inhibited in a dose-dependent fashion by forskolin. Similarly, in the xenograft model, tumor growth was also significantly reduced by forskolin treatment.
  
  
  CONCLUSIONS
  Our findings suggest that the Hh signaling pathway plays an important role in the tumorigenesis of RMS and that this pathway can be considered to be a potential molecular target of new treatment strategies for RMS.
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Takaharu
authors.initials: T
authors.lastname: Oue
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Uehara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuzawa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology* / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D014183:Transplantation, Heterologous; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D005576:Colforsin