IFN-beta is a highly potent inhibitor of gastroenteropancreatic neuroendocrine tumor cell growth in vitro
| Autor: | Leo J. Hofland, Annamaria Colao, Marlijn Waaijers, Ed Croze, Wouter W. de Herder, Giovanni Vitale, Wenda Schoordijk, Steven W. J. Lamberts, Peter M. van Koetsveld |
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| Přispěvatelé: | Internal Medicine, G., Vitale, W. W., de Herder, P. M., van Koetsveld, M., Waaijer, W., Schoordijk, E., Croze, Colao, Annamaria, S. W., Lambert, L. J., Hofland |
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
medicine.medical_specialty Cell cycle checkpoint Apoptosis Carcinoid Tumor Cell Growth Processes Receptor Interferon alpha-beta Interferon alpha-2 Biology Settore MED/13 - Endocrinologia Flow cytometry In vivo Cell Line Tumor Internal medicine Chromogranins medicine Humans RNA Messenger Gastrointestinal Neoplasms Receptors Interferon medicine.diagnostic_test Cell growth Cell Cycle Interferon-alpha Membrane Proteins Interferon-beta Cell cycle Molecular biology Recombinant Proteins Pancreatic Neoplasms pancrea Neuroendocrine Tumors Endocrinology Oncology Cell culture Chromogranin A DNA fragmentation Interferon beta-1a |
| Zdroj: | Cancer Research, 66(1), 554-562. American Association for Cancer Research Inc. |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | 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. (Cancer Res 2006; 66(1): 554-62) |
| Databáze: | OpenAIRE |
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