Alveolar II pulmonary tumor cells (A549), maintained in continuous tridimen-sional organotypic culture, were used in an attempt to investigate whether there could be a relationship of the 2′,5′-oligoadenylate (2,5A) synthetase pathway to the antiproliferative activity of interferons (IFNs) in this particular tumor cell model. IFN-α2 -β and -γ were used separately and in combinations. IFN- α2 and -γ demonstrated an inhibitory effect on the nodule growth, whereas IFN- β did not. Moreover, combinations of IFN-α2 and -γ resulted in a significant synergistic antiproliferative activity; IFN- β only potentiated slightly the effect of IFN-γ. All three IFNs induced an increase in the 2,5A synthetase activity, indicating a discrepancy with the pattern of anticellular activity. Furthermore, whereas the combination of IFN- α2 and -γ resulted in a synergistic antiproliferative effect, no synergism was observed in the induction of the enzyme. These results show that there is a lack of correlation between the sensitivity or the resistance to IFNs of A549 tumor nodules and the induction of the 2,5A synthetase activity.

Keywords:
Organotypic culture, Interferons, Antiproliferative activity, 2′,5′-Oligoadenylate synthetase
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© 1988 S. Karger AG, Basel
1988
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