title: Pegylated interferon-α2a inhibits proliferation of human liver cancer cells in vitro and in vivo.
abstract: OBJECTIVE
  We investigated the effects of pegylated interferon-α2a (PEG-IFN-α2a) on the growth of human liver cancer cells.
  
  
  METHODS
  The effect of PEG-IFN-α2a on the proliferation of 13 liver cancer cell lines was investigated in vitro. Cells were cultured with medium containing 0-4,194 ng/mL of PEG-IFN-α2a, and after 1, 2, 3, or 4 days of culture, morphologic observation and growth assay were performed. After hepatocellular carcinoma (HCC) cells (HAK-1B and KIM-1) were transplanted into nude mice, various doses of PEG-IFN-α2a were subcutaneously administered to the mice once a week for 2 weeks, and tumor volume, weight, and histology were examined.
  
  
  RESULTS
  PEG-IFN-α2a inhibited the growth of 8 and 11 cell lines in a time- and dose-dependent manner, respectively, although the 50% growth inhibitory concentrations of 7 measurable cell lines on Day 4 were relatively high and ranged from 253 ng/mL to 4,431 ng/mL. Various levels of apoptosis induction were confirmed in 8 cell lines. PEG-IFN-α2a induced a dose-dependent decrease in tumor volume and weight, and a significant increase of apoptotic cells in the tumor. Subcutaneous administration of clinical dose for chronic hepatitis C (3 μg/kg, 0.06 μg/mouse) was effective and induced about 30-50% reduction in the tumor volume and weight as compared with the control.
  
  
  CONCLUSIONS
  Although in vitro anti-proliferative effects of PEG-IFN-α2a were relatively weak, PEG-IFN-α2a induced strong anti-tumor effects on HCC cells in vivo. The data suggest potential clinical application of PEG-IFN-α2a for the prevention and treatment of HCC.
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Kusano
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Akiba
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ogasawara
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Sanada
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Yasumoto
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurita
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Todoroki
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Umeno
authors.affiliation: Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Fukuoka, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakashima
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a