4.8 Article

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

Journal

JOURNAL OF HEPATOLOGY
Volume 41, Issue 5, Pages 782-789

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2004.07.012

Keywords

angiogenesis; apoptosis; antiproliferation; consensus interferon; hepatocellular carcinoma; nude mouse

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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.

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