Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo.

We investigated the effects of pegylated IFN-alpha2b (PEG-IFN-alpha2b) on the growth of human liver cancer cells. 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. 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. 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.

Citation

Hirohisa Yano, Sachiko Ogasawara, Seiya Momosaki, Jun Akiba, Sakiko Kojiro, Suguru Fukahori, Hironori Ishizaki, Keitaro Kuratomi, Yuji Basaki, Shinji Oie, Michihiko Kuwano, Masamichi Kojiro. Growth inhibitory effects of pegylated IFN alpha-2b on human liver cancer cells in vitro and in vivo. Liver international : official journal of the International Association for the Study of the Liver. 2006 Oct;26(8):964-75

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PMID: 16953837

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