Human lung cancer nodules in organotypic culture: no evidence of correlation between the antiproliferative effects of interferons and the induction of 2',5'-oligoadenylate synthetase.
Alveolar II pulmonary tumor cells (A549), maintained in continuous tridimensional 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-alpha 2, -beta and -gamma were used separately and in combinations. IFN-alpha 2 and -gamma demonstrated an inhibitory effect on the nodule growth, whereas IFN-beta did not. Moreover, combinations of IFN-alpha 2 and -gamma resulted in a significant synergistic antiproliferative activity; IFN-beta only potentiated slightly the effect of IFN-gamma. 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-alpha 2 and -gamma 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.
Martyré
M C
MC
U 196 INSERM, Institut Curie, Paris, France.
Beaupain
R
R
Falcoff
E
E
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology*; D011650:Pulmonary Alveoli; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007370:Interferon Type I; D007371:Interferon-gamma; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase