title: Interferon alpha receptors are important for antiproliferative effect of interferon-alpha against human hepatocellular carcinoma cells.
abstract: OBJECTIVE
  Interferon (IFN)-alpha is a promising drug for the prevention and treatment of hepatocellular carcinoma (HCC). We reported that responders to IFN-alpha/5-fluorouracil combination therapy expressed higher IFN alpha receptor (IFNAR)2 in tumor. Herein we studied involvement of IFNARs in response to IFN-alpha in HCC cells.
  
  
  METHODS
  IFN-alpha sensitivity and expression of IFNARs were studied in six HCC cell lines (HuH7, PLC/PRF/5, HLE, HLF, HepG2, Hep3B) using growth-inhibitory and RT-PCR, Western blot assays. Short interfering RNAs (SiRNAs) against IFNAR1 and 2 were used to analyze the role of the IFNARs in IFN-alpha's effect and signal transduction.
  
  
  RESULTS
  The expressions of IFNAR1 and 2c mRNAs were higher in PLC/PRF/5 cells than those in other cell lines, and PLC/PRF/5 cells expressed abundant IFNAR2c on their cell membrane. When we examined the sensitivity of the HCC cell lines to the growth-inhibitory effect of IFN-alpha, PLC/PRF/5 exhibited a significant response, while the other cells were much more resistant. Knockdown of either IFNAR1 or 2 using siRNAs suppressed the IFN-alpha's signal transduction (2.5-fold), and decreased the growth-inhibitory effect (down by 69.9% and 67.3%).
  
  
  CONCLUSIONS
  The results suggest that the expression of IFNAR1 and IFNAR2c independently are important for the antiproliferative effect of IFN-alpha in HCC cells.
authors.affiliation: Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Bazarragchaa
authors.initials: B
authors.lastname: Damdinsuren
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.forename: Takehiro
authors.initials: T
authors.lastname: Noda
authors.forename: Javzandulam
authors.initials: J
authors.lastname: Natsag
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takeda
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Keizo
authors.initials: K
authors.lastname: Dono
authors.forename: Morito
authors.initials: M
authors.lastname: Monden