Interferon-αCon1 suppresses proliferation of liver cancer cell lines in vitro and in vivo

被引:28
作者
Hisaka, T [1 ]
Yano, H [1 ]
Ogasawara, S [1 ]
Momosaki, S [1 ]
Nishida, N [1 ]
Takemoto, Y [1 ]
Kojiro, S [1 ]
Katafuchi, Y [1 ]
Kojiro, M [1 ]
机构
[1] Kurume Univ, Dept Pathol, Sch Med, Res Ctr Innovat Canc Therapy,Century COE Program, Kurume, Fukuoka 8300011, Japan
关键词
angiogenesis; apoptosis; antiproliferation; consensus interferon; hepatocellular carcinoma; nude mouse;
D O I
10.1016/j.jhep.2004.07.012
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: We investigated the effects of consensus interferon (IFN-alphaCon1), a nonnaturally occurring type I interferon with higher specific activity than other type I IFNs, on the growth of human liver cancer cells. Methods: The effect of IFN-alphaCon1 on the proliferation of 13 liver cancer cell lines was investigated in vitro. Hepatocellular carcinoma (HCC) cells (KIM-1 and HAK-1B) were transplanted subcutaneously into the back of nude mice, then IFN-alphaCon1 was subcutaneously administered to the mice once a day for 2 weeks, and tumor volume and histology were examined. Results: IFN-alphaCon1 expressed a dose-dependent growth inhibitory effect in all cell lines in vitro. KIM-1 tumor volume in mice that received 0.01 mug (10(4) IU)/mouse/day of IFN-alphaCon1 (similar to the clinical dose for chronic hepatitis C) was 62% of the control, 0.1 mug/mouse/day resulted in 26%, and 1 mug/mouse/day resulted in 10%. HAK-1B tumor volume under the same treatment was 61, 24 and 0% of the control, respectively. The number of apoptotic cells significantly increased and the number of blood vessels significantly decreased with the increase in IFN-alphaCon1 dose. Conclusions: IFN-alphaCon1 suppressed HCC growth in nude mice. These data indicate the potential clinical application of IFN-aConl in the prevention and treatment of HCC. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:782 / 789
页数:8
相关论文
共 46 条
[1]   The in vivo apoptotic effect of interferon alfa-2b on rat preneoplastic liver involves Bax protein [J].
Alvarez, M ;
Cerliani, JP ;
Monti, J ;
Carnovale, C ;
Ronco, MT ;
Pisani, G ;
Lugano, MC ;
Carrillo, MC .
HEPATOLOGY, 2002, 35 (04) :824-833
[2]  
[Anonymous], 1984, ACTA HEPATOL JPN
[3]  
BISCEGLIE AM, 1991, AM J GASTROENTEROL, V86, P335
[4]   The biologic activity and molecular characterization of a novel synthetic interferon-alpha species, consensus interferon [J].
Blatt, LM ;
Davis, JM ;
Klein, SB ;
Taylor, MW .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1996, 16 (07) :489-499
[5]   Impact of HBV HCV and GBV-C/HGV on hepatocellular carcinomas in Europe:: results of a European concerted action [J].
Bréchot, C ;
Jaffredo, F ;
Lagorce, D ;
Gerken, G ;
zum Büschenfelde, KM ;
Papakonstontinou, A ;
Hadziyannis, S ;
Romeo, R ;
Colombo, M ;
Rodes, J ;
Bruix, J ;
Williams, R ;
Naoumov, N .
JOURNAL OF HEPATOLOGY, 1998, 29 (02) :173-183
[6]   ROLE OF G0-G1 ARREST IN THE INHIBITION OF TUMOR-CELL GROWTH BY INTERFERON [J].
CREASEY, AA ;
BARTHOLOMEW, JC ;
MERIGAN, TC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (03) :1471-1475
[7]  
Dinney CPN, 1998, CANCER RES, V58, P808
[8]   HUMAN-LYMPHOBLASTOID INTERFERON - INVITRO AND INVIVO STUDIES IN HEPATOCELLULAR-CARCINOMA [J].
DUNK, AA ;
IKEDA, T ;
PIGNATELLI, M ;
THOMAS, HC .
JOURNAL OF HEPATOLOGY, 1986, 2 (03) :419-429
[9]  
*GASTR TUM STUD GR, 1990, CANCER, V66, P135
[10]   CYTOKINE THERAPEUTICS - LESSONS FROM INTERFERON-ALPHA [J].
GUTTERMAN, JU .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (04) :1198-1205