IFN-α controls hormone secretion and symptoms in human gastroenteropancreatic neuroendocrine tumors (GEP-NET) but it rarely induces a measurable tumor size reduction. The effect of other type I IFNs, e.g., IFN-β, has not been evaluated. We compared the antitumor effects of IFN-α and IFN-β in BON cells, a functioning human GEP-NET cell line. As determined by quantitative reverse transcription-PCR analysis and immunocytochemistry, BON cells expressed the active type I IFN receptor mRNA and protein (IFNAR-1 and IFNAR-2c subunits). After 3 and 6 days of treatment, IFN-β significantly inhibited BON cell growth in a time- and dose-dependent manner. IC50 and maximal inhibitory effect on day 6 were 8 IU/mL and 98%, respectively. In contrast, the effect of IFN-α resulted significantly in a less potent effect (IC50: 44 IU/mL, maximal inhibition: 26%). IFN-α induced only cell cycle arrest, with an accumulation of the cells in S phase. IFN-β, apart from a more potent delay in S-G2-M phase transit of the cell cycle, also induced a strong stimulation of apoptosis, evaluated by flow cytometry (Annexin V and 7-AAD) and measurement of the DNA fragmentation. Besides, only IFN-β severely suppressed chromogranin A levels in the medium from BON cells after 6 days of treatment In conclusion, IFN-β is much more potent, compared with IFN-α, in its inhibitory effect on GEP-NET cell proliferation in vitro through the induction of apoptosis and cell cycle arrest. Further studies are required to establish whether IFN-β has comparable potent tumor growth inhibitory effects in vivo.
ASJC Scopus subject areas
- Cancer Research