RESUMO
We have studied the antiviral activities of five recombinant interferon-alpha (IFN-alpha) subtypes, namely IFN-alpha1, -alpha2, -alpha5, -alpha8 and -alpha10, in eight human liver cancer cell lines. The relative antiviral activities, expressed in terms of the mean 50% inhibitory concentration (IC50), were different for each cell line. In general, IFN-alpha8 was the most potent, IFN-alpha2, -alpha5, and -alpha10 were intermediately active, and IFN-alpha1 was the least potent in the all cell lines. The observed differences between the IC50s of IFN-alpha1 and -alpha8 ranged from 250- to 2200-fold in these cell lines. Thus, the ranking order of relative antiviral activity was similar but the sensitivity to the subtypes was different among these cell lines. The relative antiviral activities of the subtypes were associated with the induction of 2',5'-oligoadenylate synthetase (2',5'-OAS) in the typical hepatocellular carcinoma cell line HAK-3 but not in the cell line KYN-3. Next, we examined for synergistic antiviral activity induced by IFN-alpha2 and -alpha8 that has been reported for the hepatocellular carcinoma cell line, HepG2. Synergism was observed in three of the eight liver cell lines at an IFN-alpha2 to -alpha8 ratio of 60:40, and is considered to reflect the synergistic induction of 2',5'-OAS.
RESUMO
Here we report on the anti-tumor effects of five interferon (IFN)-alpha subtypes, alpha1, alpha2, alpha5, alpha8, and alpha10 in chronic myelogenous leukaemia (CML)-derived cell lines. All of the CML cells can respond to IFN-alpha although the anti-tumor effects of IFN-alpha depend on the target cell and on the type of IFN-alpha subtype used. Proliferation assays showed that IFN-alpha8 was substantially more effective than the other four IFN-alpha subtypes. IFN-alpha8 was the most potent at upregulating immunomodulatory molecule expression while IFN-alpha1 was least potent. These data indicate in vitro distinctions between IFN-alpha subtypes that should be appreciated more in the clinic.
