title: Cyclopamine blocked the growth of colorectal cancer SW116 cells by modulating some target genes of Gli1 in vitro.
abstract: OBJECTIVE
  Hedgehog (Hh) pathway has been considered as a therapy target for various cancer entities. However, its mechanism in colorectal cancer is still unclear.
  
  
  METHODS
  We analyzed the expression of Hh pathway members in colorectal adenomas and cancer cell lines and then studied its relationship with survival of colorectal cancer cells through inhibiting Hh pathway by cyclopamine. Moreover, we studied the regulation of Gli1 on insulin-like growth factor binding protein 6 (IGFBP6) and B-cell CLL/lymphoma 2 (Bcl-2) genes at the level of transcription by XChIP and cyclopamine inhibition assay.
  
  
  RESULTS
  Sonic hedgehog (Shh), Smoothened (Smo), patched (Ptch) and Gli1 genes mRNA were expressed in SW116 cells. Gli1 bound to promoter regions of Bcl-2 and IGFBP6 genes, cyclopamine inhibited proliferation and induced apoptosis through inhibiting the transcriptions of IGFBP6 (p=0.003), proliferating cell nuclear antigen (PCNA) (p=0.014) and Bcl-2 (p=0.013), and increasing that of BCL2-associated X protein (Bax) and BCL2-antagonist/killer 1 (Bak1) (p=0.003 and 0.001, respectively) in SW116 cells.
  
  
  CONCLUSIONS
  Hh pathway is aberrant activation in part colorectal carcinomas cell lines and its inhibitor may be an effectual agent for colorectal cancer chemoprevention. It may be one of the mechanisms that Gli1 maintained cell survival by binding the promoter regions and facilitating transcription of IGFBP6 and Bcl-2 genes.
authors.affiliation: Department of Gastroenterology, Tongji University, Shanghai, China.
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Wu
authors.forename: Xuan-Fu
authors.initials: XF
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Pei-Qin
authors.initials: PQ
authors.lastname: Niu
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Guo-Yong
authors.initials: GY
authors.lastname: Hu
authors.forename: Xing-Peng
authors.initials: XP
authors.lastname: Wang
authors.forename: Chuan-Yong
authors.initials: CY
authors.lastname: Guo
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019254:Genes, bcl-2 / Q000235:genetics; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014704:Veratrum Alkaloids / Q000494:pharmacology*; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D018976:Insulin-Like Growth Factor Binding Protein 6; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; C000541:cyclopamine