IFN-β Is a Highly Potent Inhibitor of Gastroenteropancreatic Neuroendocrine Tumor Cell Growth In vitro

Abstract

IFN-A 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-B, has not been evaluated. We compared the antitumor effects of IFN-A and IFN-B 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-B significantly inhibited BON cell growth in a time-and dose-dependent manner. IC 50 and maximal inhibitory effect on day 6 were 8 IU/mL and 98%, respectively. In contrast, the effect of IFN-A resulted significantly in a less potent effect (IC 50 : 44 IU/mL, maximal inhibition: 26%). IFN-A induced only cell cycle arrest, with an accumulation of the cells in S phase. IFN-B, apart from a more potent delay in S-G 2 -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-B severely suppressed chromogranin A levels in the medium from BON cells after 6 days of treatment. In conclusion, IFN-B is much more potent, compared with IFN-A, 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-B has comparable potent tumor growth inhibitory effects in vivo. (Cancer Res 2006; 66(1): 554-62)

Effects of type I interferons on IGF-mediated autocrine/paracrine growth of human neuroendocrine tumor cells

“…Notwithstanding IFN-␤ half-life (1 h) is shorter than that of IFN-␣ (4 -7 h), several studies showed that IFN-␤ has more potent antitumor effects than IFN-␣, via the activation of apoptosis (6,8,12,16,27,(31)(32)(33). In addition, new strategies could improve in future the pharmacokinetic and pharmacodynamic profile of IFN-␤, like the pegylated formulation (21).…”

“…Similarly, we observed a more potent antiproliferative activity after treatment with IFN-␤ than IFN-␣ in the NET cell line BON. This effect is likely related to the fact that IFN-␣ induced cell cycle arrest only, whereas both apoptosis and a more potent delay in S-G 2 /M phase transit of the cell cycle were responsible for IFN-␤-mediated growth suppression in BON cells (32).…”

“…In a recent study, we have compared the antitumor effects of interferon (IFN)-␣ and IFN-␤ in BON cells (32). The antiproliferative activity of IFN-␤ is considerably more potent than IFN-␣.…”

An engineered avian-origin influenza A virus for pancreatic ductal adenocarcinoma virotherapy

“…IFN-a and -b are multifunctional cytokines that have shown efficacy in the treatment in vitro and in vivo of several tumours types including PDAs (Booy et al, 2014;Lindner et al, 1997;Tomimaru et al, 2011;Vitale et al, 2006Vitale et al, , 2007.…”

Synergistic antitumor effect of interferon-ß with gemcitabine in interferon-α-non-responsive pancreatic cancer cells

“…The reported antitumor activity of IFN-ß exceeds that of IFN-· in several kinds of cancers (25)(26)(27)(28)(29). We compared previously the antitumor of IFN-ß to IFN-· on HCC and reported that IFN-ß had synergistic antitumor effect with anticancer drugs even in HCC cells with weak IFNAR2 expression level (30).…”