title: XAV939, a tankyrase 1 inhibitior, promotes cell apoptosis in neuroblastoma cell lines by inhibiting Wnt/β-catenin signaling pathway.
abstract: BACKGROUND
  Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. The present treatment including surgery, chemotherapy and radiation, which have only 40% long-term cure rates, and usually cause tumor recurrence. Thus, looking for new effective and less toxic therapies has important significance. XAV939 is a small molecule inhibitor of tankyrase 1(TNKS1). The objective of this study is to investigate the effect of XAV939 on the proliferation and apoptosis of NB cell lines, and the related mechanism.
  
  
  METHODS
  In the present study, we used both XAV939 treatment and RNAi method to demonstrate that TNKS1 inhibition may be a potential mechanism to cure NB. MTT method was used for determining the cell viability and the appropriate concerntration for follow-up assays. The colony formation assay, Annexin V staining and cell cycle analysis were used for detecting colony forming ability, cell apoptosis and the percentage of different cell cycle. The Western blot was used for detecting the expression of key proteins of Wnt/ beta-catenin (Wnt/β-catenin) signaling pathway.
  
  
  RESULTS
  The results showed that TNKS1 inhibition decreased the viability of SH-SY5Y, SK-N-SH and IMR-32 cells, induced apoptosis in SH-SY5Y as well as SK-N-SH cells, and led to the accumulation of NB cells in the S and G2/M phase of the cell cycle. Moreover, we demonstrated TNKS1 inhibition may in part blocked Wnt/β-catenin signaling and reduced the expression of anti-apoptosis protein. Finally, we also demonstrated that TNKS1 inhibition decreased colony formation in vitro.
  
  
  CONCLUSIONS
  These findings suggested that TNKS1 may be a potential molecule target for the treatment of NB.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Tian
authors.forename: Wei-Jian
authors.initials: WJ
authors.lastname: Hou
authors.forename: Yan
authors.initials: Y
authors.lastname: Fang
authors.forename: Jun
authors.initials: J
authors.lastname: Fan
authors.forename: Hao
authors.initials: H
authors.lastname: Tong
authors.affiliation: Department of Tissue Engineering, College of Basic Medical Sciences, China Medical University, Shenyang 110001, PR China. shuling_bai@126.com.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Bai
authors.forename: Qu
authors.initials: Q
authors.lastname: Chen
authors.forename: He
authors.initials: H
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D038501:Tankyrases / Q000037:antagonists & inhibitors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D038501:Tankyrases; C544261:XAV939; C418109:TNKS protein, human