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We investigated the effects of interferon-β(IFN-β) on the growth of human liver cancer cells. The effects of IFN-βwith or without 5-fluorouracil (5-FU) on the proliferation of 13 liver cancer cell lines were investigated in vitro. Chronologic change in IFN-αreceptor 2 (IFNAR-2) expression was monitored in hepatocellular carcinoma (HCC) cells (HAK-1B) cultured with IFN-β. After HAK-1B cells were transplanted into nude mice, various doses of IFN-βwere administered, and the tumor volume, weight, histology, tumor blood vessel, and angiogenesis factor expression were examined. IFN-βinhibited the growth of 11 cell lines with apoptosis in a dose-dependent and time-dependent manner. With IFN-β, IFNAR-2 expression in HAK-1B cells was significantly downregulated from 6 to 12 h. IFN-βinduced a dose-dependent decrease in tumor volume and weight and a significant increase of apoptosis in the tumor. Both basic fibroblast growth factor (bFGF) and blood vessel number in the tumor decreased only in mice receiving the lowest dose (1000 IU) of IFN-β. IFN-βwith 10 μM of 5-FU frequently induced synergistic antiproliferative effects. IFN-βwith or without 5-FU induces strong antitumor effects in HCC cells, and we conclude that IFN-βis useful for the prevention and treatment of HCC. [ABSTRACT FROM AUTHOR]

We investigated the effects of pegylated (PEG)-IFN-α2b on α-fetoprotein (AFP) expression as demonstrated by protein and mRNA levels in six human hepatocellular carcinoma (HCC) cell lines. The number of KIM-1 cells in culture with PEG-IFN-α2b decreased between 24 amd 240 h, whereas the levels of intracellular and secreted AFP per cellular protein increased (except at 192 h), with levels 1.9-fold and 2.9-fold higher at maximum, respectively, than cells without PEG-IFN-α2b (control). The mRNA level increased between 72 and 192 h, when the level was 3-fold higher than that of the control. In the 72-h culture with 40–5000 IUmL PEG-IFN-α2b, there were dose-dependent increases in AFP protein and mRNA expression and dose-dependent decrease in cell number resulting from apoptosis and blockage of the cell cycle at the S-phase. The rate of fucosylated AFP in the cell lysate decreased in a dose-dependent and time-dependent manner. In the PEG-IFN-α2b culture of the other five HCC cell lines, cell proliferation was suppressed, but the expressions of AFP protein and mRNA increased in only two cell lines, and suppression of cell proliferation was not related to the increase in AFP expressions. Our findings demonstrated that PEG-IFN-α2b induces an increase in AFP expression at both the protein and mRNA levels. [ABSTRACT FROM AUTHOR]