Interferon alpha receptors are important for antiproliferative effect of interferon-alpha against human hepatocellular carcinoma cells.
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.
Damdinsuren
Bazarragchaa
B
Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Nagano
Hiroaki
H
Wada
Hiroshi
H
Noda
Takehiro
T
Natsag
Javzandulam
J
Marubashi
Shigeru
S
Miyamoto
Atsushi
A
Takeda
Yutaka
Y
Umeshita
Koji
K
Doki
Yuichiro
Y
Dono
Keizo
K
Monden
Morito
M