title: In vitro regulation of hepatocellular carcinoma cell viability, apoptosis, invasion, and AEG-1 expression by LY294002.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, and is characterized by advanced clinical stages at diagnosis and very poor prognosis.
  
  
  METHODS
  This study investigated the effects of PI3K inhibitor, LY294002, on suppression of astrocyte elevated gene-1 (AEG-1) and regulation of HCC cell viability, apoptosis, and invasion in vitro. Cell lines derived from normal liver and HCC were treated with LY294002 and evaluated by RT-PCR, western blot, cell viability, migration, and invasion assays.
  
  
  RESULTS
  The data showed that AEG-1 mRNA and protein were overexpressed in HCC cells, compared to the normal liver cells. LY294002 treatment of HCC cells significantly reduced tumor cell viability, but promoted apoptosis. Tumor cell migration and invasion assays showed that LY294002 treatment also decreased the capacity of HCC cell migration and invasion. Molecularly, LY294002 treatment down-regulated AEG-1 expression, AKT and GSK3β phosphorylation, and expression of cyclinD1, CDK4, VEGF and Bcl2, but up-regulated Bax and c-Myc expression.
  
  
  CONCLUSIONS
  The data from this study demonstrated usefulness of LY294002 for effective control of HCC. Future studies should investigate the effects of LY294002 on HCC cells in vivo before initiating clinical trials in HCC patients.
authors.affiliation: Department of Hepatobillary and Pancreatic Surgery, The First Norman Bethune Hospital of Jilin University, Changchun 130021, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Hepatobillary and Pancreatic Surgery, The First Norman Bethune Hospital of Jilin University, Changchun 130021, China.
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Xie
authors.affiliation: Department of Hepatobillary and Pancreatic Surgery, The First Norman Bethune Hospital of Jilin University, Changchun 130021, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Geng
authors.affiliation: Department of Hepatobillary and Pancreatic Surgery, The First Norman Bethune Hospital of Jilin University, Changchun 130021, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Hepatobillary and Pancreatic Surgery, The First Norman Bethune Hospital of Jilin University, Changchun 130021, China. Electronic address: majian10@mails.jlu.edu.cn.
authors.forename: Guang-Yi
authors.initials: GY
authors.lastname: Wang
authors.affiliation: Department of Hepatobillary and Pancreatic Surgery, The First Norman Bethune Hospital of Jilin University, Changchun 130021, China. Electronic address: guoyuelv@sina.com.
authors.forename: Guo-Yue
authors.initials: GY
authors.lastname: Lv
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008565:Membrane Proteins; D009025:Morpholines / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000235:genetics; D016601:RNA-Binding Proteins; D014407:Tumor Cells, Cultured
chemical_list: D015815:Cell Adhesion Molecules; D002867:Chromones; D004791:Enzyme Inhibitors; C483039:MTDH protein, human; D008565:Membrane Proteins; D009025:Morpholines; D016601:RNA-Binding Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one