Effects of α-interferon on insulin-like growth factor-I, insulin-like growth factor-II and insulin-like growth factor binding protein-3 secretion by a human lung cancer cell line in vitro

The aim of our study was to evaluate the effect of α-interferon (α-IFN) on cell growth and on the different IGF system components in a human non-small cell lung cancer line (Calu-6) in vitro. Our results confirm the release of IGF-I and IGF-II by these cells. The amount of IGF-II in conditioned media (10.25±3.95 nM/10 6 cells, mean±SE) was more than 10-fold higher than that of IGF-I. α-IFN treatment reduced IGF-II levels in the media, with a maximal effect between 1 and 10 U/ml (Δ% of control: −31 and −55%, respectively, p<0.05). IGF-I was significantly reduced at 0.5 U/ml ( p <0.01). No difference, however, was observed in IGF mRNA expression between untreated and α-IFN treated cells. An increase in IGF-I and IGF-II intracellular levels in α-IFN treated cultures was observed, suggesting that α-IFN can regulate the transfer of these peptides into the cells. Furthermore, IGF type-I and particularly type-II receptor expression was increased after α-IFN treatment. IGFBP-3 was detected only in trace amounts in the conditioned media; however, it showed an increase after α-IFN treatment (+110% at 1 U/ml). IGFBP-3 mRNA expression showed a slight increase after treatment with 1 and 10 U/ml. α-IFN (1-10 U/ml) reduced the stimulatory effect of IGF-I on cell replication ( p <0.01), inhibited ( p <0.01) cell replication in untreated and in fetal calf serum (FCS)-stimulated cells, and increased apoptosis in Calu-6 cells. Our data suggest that α-IFN may exert its effects at the cellular level in part through modification of the local IGF system.