title: Hepatopoietin Cn suppresses apoptosis of human hepatocellular carcinoma cells by up-regulating myeloid cell leukemia-1.
abstract: OBJECTIVE
  To investigate the role of hepatopoietin Cn (HPPCn) in apoptosis of hepatocellular carcinoma (HCC) cells and its mechanism.
  
  
  METHODS
  Two human HCC cell lines, SMMC7721 and HepG2, were used in this study. Immunostaining, Western blotting and enzyme linked immunosorbent assay were conducted to identify the expression of HPPCn and the existence of an autocrine loop of HPPCn/HPPCn receptor in SMMC7721 and HepG2. Apoptotic cells were detected using fluorescein isothiocyanate (FITC)-conjugated Annexin V and propidium iodide.
  
  
  RESULTS
  The HPPCn was highly expressed in human HCC cells and secreted into culture medium (CM). FITC-labeled recombinant human protein (rhHPPCn) could specifically bind to its receptor on HepaG2 cells. Treatment with 400 ng/mL rhHPPCn dramatically increased the viability of HCC-derived cells from 48.1% and 36.9% to 85.6% and 88.4%, respectively (P < 0.05). HPPCn silenced by small-interfering RNA reduced the expression and secretion of HPPCn and increased the apoptosis induced by trichostatin A. Additionally, HPPCn could up-regulate the expression of myeloid cell leukemia-1 (Mcl-1) in HCC cells via mitogen-activated protein kinase (MAPK) and sphingosine kinase-1.
  
  
  CONCLUSIONS
  HPPCn is a novel hepatic growth factor that can be secreted to CM and suppresses apoptosis of HCC cells by up-regulating Mcl-1 expression.
authors.affiliation: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Zhang
authors.forename: Da-Jin
authors.initials: DJ
authors.lastname: Zhang
authors.forename: Chu-Tse
authors.initials: CT
authors.lastname: Wu
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Wang
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Cui
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*; D000099157:Sphingosine Kinase
chemical_list: D017228:Hepatocyte Growth Factor; D006877:Hydroxamic Acids; D020929:Mitogen-Activated Protein Kinase Kinases; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D017853:Phosphotransferases (Alcohol Group Acceptor); D011500:Protein Synthesis Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D019859:Proto-Oncogene Proteins c-met; D011994:Recombinant Proteins; D000099157:Sphingosine Kinase; C012589:trichostatin A