Interferon-alphaCon1 suppresses proliferation of liver cancer cell lines in vitro and in vivo.
OBJECTIVE
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 microg (10(4)IU)/mouse/day of IFN-alphaCon1 (similar to the clinical dose for chronic hepatitis C) was 62% of the control, 0.1microg/mouse/day resulted in 26%, and 1 microg/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-alphaCon1 in the prevention and treatment of HCC.
Hisaka
Toru
T
Department of Pathology, Kurume University School of Medicine, Research Center of Innovative Cancer Therapy of the 21 Century COE Program for Medical Science, Kurume University, 67 Asahi-machi, 830-0011 Kurume, Japan.
Yano
Hirohisa
H
Ogasawara
Sachiko
S
Momosaki
Seiya
S
Nishida
Naoyo
N
Takemoto
Yumi
Y
Kojiro
Sakiko
S
Katafuchi
Yuno
Y
Kojiro
Masamichi
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000473:pathology; D001653:Bile Ducts, Intrahepatic; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D016898:Interferon-alpha; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011994:Recombinant Proteins
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins; C050739:interferon alfacon-1