title: Down-regulation of HDGF Inhibits the Growth of Hepatocellular Carcinoma Cells In Vitro and In Vivo.
abstract: BACKGROUND
  Hepatoma-derived growth factor (HDGF) is a growth factor of various malignant diseases. However, the in vivo effects of HDGF suppression targeting for hepatocellular carcinoma (HCC) have not been clarified to date.
  
  
  METHODS
  We stably transfected HDGF shRNA into SK-HEP-1 human HCC cells and investigated the effects of HDGF reduction on HCC growth using a cell proliferation assay and a murine xenograft model. The effects of HDGF reduction on VEGF expression and in vivo angiogenesis were also investigated with real-time PCR and immunostaining analyses, respectively.
  
  
  RESULTS
  HDGF reduction resulted in a decreased proliferative activity of SK-HEP-1 cells both in vitro and in vivo. The in vivo anti-tumor effects of HDGF were particularly higher than that expected in vitro. HDGF-reduction suppressed VEGF expression in SK-HEP-1 cells and in vivo angiogenesis of developed tumors.
  
  
  CONCLUSIONS
  These findings suggest that targeted inhibition of HDGF may be a novel anti-HCC therapy.
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan enomoto@hyo-med.ac.jp.
authors.forename: Hirayuki
authors.initials: H
authors.lastname: Enomoto
authors.affiliation: Department of Gastroenterology and Hepatology, Nissay Hospital, Nishi-ku, Osaka, Japan.
authors.forename: Hideji
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Hepatology and Infectious Diseases, the Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, P.R. China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Iwata
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nishikawa
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Takata
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yoh
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Ishii
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Takashima
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Aizawa
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Ikeda
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iijima
authors.affiliation: Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C051610:hepatoma-derived growth factor
keywords: Hepatoma-derived growth factor; VEGF; angiogenesis; hepatocellular carcinoma; targeted therapy; xenograft model