Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo.
OBJECTIVE
We investigated the effects of pegylated IFN-alpha2b (PEG-IFN-alpha2b) on the growth of human liver cancer cells.


METHODS
The effect of PEG-IFN-alpha2b on the proliferation of 13 liver cancer cell lines was investigated in vitro. Chronological changes in growth and IFN-alpha receptor-2 (IFNAR-2) expression were monitored in hepatocellular carcinoma (HCC) cells (HAK-1B) cultured with PEG-IFN-alpha2b. After HAK-1B cells were transplanted into nude mice, various doses of PEG-IFN-alpha2b or IFN-alpha2b were administered, and tumor volume, weight, histology, and IFNAR-2 expression were examined.


RESULTS
PEG-IFN-alpha2b inhibited the growth of nine cell lines with apoptosis in a dose- and time-dependent manner. Continuous contact with PEG-IFN-alpha2b induced time-dependent growth inhibition and down-regulation of IFNAR-2 expression. PEG-IFN-alpha2b induced a dose-dependent decrease in tumor volume and weight, a significant increase of apoptotic cells, and a decrease in IFNAR-2 expression in the tumor. The clinical dose for chronic hepatitis C was also effective. The antitumor effect of PEG-IFN-alpha2b was significantly stronger than that of non-PEG-IFN-alpha2b in vivo.


CONCLUSIONS
Continuous contact with PEG-IFN-alpha2b induces strong antitumor effects and the down-regulation of IFNAR-2 in HCC cells. The data suggest potential clinical application of PEG-IFN-alpha2b for the prevention and treatment of HCC.
Yano
Hirohisa
H
Department of Pathology, Kurume University School of Medicine, Kurume, Japan. hiroyano@med.kurume-u.ac.jp
Ogasawara
Sachiko
S
Momosaki
Seiya
S
Akiba
Jun
J
Kojiro
Sakiko
S
Fukahori
Suguru
S
Ishizaki
Hironori
H
Kuratomi
Keitaro
K
Basaki
Yuji
Y
Oie
Shinji
S
Kuwano
Michihiko
M
Kojiro
Masamichi
M
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011092:Polyethylene Glycols; D053633:Receptor, Interferon alpha-beta / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000276:immunology; D011994:Recombinant Proteins
C508033:IFNAR2 protein, human; C508034:Ifnar2 protein, mouse; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D017471:Receptors, Interferon; D011994:Recombinant Proteins; C120411:interferon receptor, type II; D053633:Receptor, Interferon alpha-beta; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b