title: Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses vasculogenic mimicry and proliferation of highly aggressive pancreatic cancer PaTu8988 cells.
abstract: BACKGROUND
  Pancreatic cancer is one of the most aggressive human malignancies with a extremely low 5-year survival rate. Hence, the search for more effective anti-pancreatic cancer agents is urgent.
  
  
  METHODS
  PaTu8988 pancreatic cancer cells were treated with different concentrations of suberoylanilide hydroxamic acid (SAHA), cell survival, proliferation, migration and vasculogenic mimicry (VM) were analyzed. Associated signaling changes were also analyzed by RT-PCR and Western blots.
  
  
  RESULTS
  Here, we reported that SAHA, a histone deacetylase inhibitor (HDACi), exerted significant inhibitory efficiency against pancreatic cancer cell survival, proliferation, migration and VM. SAHA dose-dependently inhibited PaTu8988 pancreatic cancer cell growth with the IC-50 of 3.4 ± 0. 7 μM. Meanwhile, SAHA suppressed PaTu8988 cell cycle progression through inducing G2/M arrest, which was associated with cyclin-dependent kinase 1 (CDK-1)/cyclin-B1 degradation and p21/p27 upregulation. Further, SAHA induced both apoptotic and non-apoptotic death of PaTu8988 cells. Significantly, SAHA suppressed PaTu8988 cell in vitro migration and cell-dominant tube formation or VM, which was accompanied by semaphorin-4D (Sema-4D) and integrin-β5 down-regulation. Our evidences showed that Akt activation might be important for Sema-4D expression in PaTu8988 cells, and SAHA-induced Sema-4D down-regulation might be associated with Akt inhibition.
  
  
  CONCLUSIONS
  This study is among the first to report the VM formation in cultured human pancreatic cancer cells. And we provided strong evidence to suggest that SAHA executes significant anti-VM efficiency in the progressive pancreatic cancer cells. Thus, SAHA could be further investigated as a promising anti-pancreatic cancer agent.
authors.forename: Xing-dong
authors.initials: XD
authors.lastname: Xu
authors.forename: Lan
authors.initials: L
authors.lastname: Yang
authors.forename: Li-yun
authors.initials: LY
authors.lastname: Zheng
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Pan
authors.forename: Zhi-fei
authors.initials: ZF
authors.lastname: Cao
authors.forename: Zhi-qing
authors.initials: ZQ
authors.lastname: Zhang
authors.forename: Quan-sheng
authors.initials: QS
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, the Third Hospital affiliated to Soochow University, Changzhou City 213003, Jiangsu, China. dryangbosz@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Cong
authors.initials: C
authors.lastname: Cao
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat; D016203:CDC2 Protein Kinase; D006655:Histone Deacetylases