Type I interferons in the treatment of pancreatic cancer: Mechanisms of action and role of related Receptors

Giovanni Vitale, C. H J Van Eijck, Peter M. Van Koetsveld Ing, Joris I. Erdmann, E. J M Speel, Katy Van Der Wansem Ing, Diana M. Mooij, Annamaria Colao, Gaetano Lombardi, Ed Croze, S. W J Lamberts, Leo J. Hofland

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: We evaluated the role of type I interferons (IFNs) and IFN receptors in the regulation of cell growth in 3 human pancreatic adenocarcinoma cell lines (BxPC-3, MiaPaCa-2, and Panc-1). BACKGROUND: Chemotherapy and radiotherapy have a marginal role in the management of pancreatic adenocarcinoma. The addition of IFN-α showed promising results in early clinical trials. METHODS: Cell proliferation and apoptosis were evaluated by DNA measurement and DNA fragmentation, respectively. Type I IFN receptor (IFNAR-1 and IFNAR-2 subunits) was determined by quantitative RT-PCR and immunocytochemistry. Cell cycle distribution was evaluated by propidium iodide staining and flow-cytometric analysis. RESULTS: The incubation with IFN-β for 6 days showed a potent inhibitory effect on the proliferation of BxPC-3 (IC50, 14 IU/mL) and MiaPaCa-2 (IC50, 64 IU/mL). The inhibitory effect of IFN-β was stronger than IFN-α in all 3 cell lines and mainly modulated by the stimulation of apoptosis, although cell cycle arrest was induced as well. The expression of the type I IFN receptors was significantly higher in BxPC-3 (the most sensitive cell line to IFN) and mainly localized on the membrane, whereas in Panc-1 (the most resistant cell line) about 60% to 70% of cells were negative for IFNAR-2c with a mainly cytoplasmic staining for IFNAR-2c. CONCLUSION: The antitumor activity of IFN-β is more potent than IFN-α in pancreatic cancer cell lines through the induction of apoptosis. Further studies should investigate in vivo whether the intensity and distribution of IFNAR-1 and IFNAR-2c may predict the response to therapy with IFN-α and IFN-β in pancreatic cancer.

Original languageEnglish
Pages (from-to)259-268
Number of pages10
JournalAnnals of Surgery
Issue number2
Publication statusPublished - Aug 2007

ASJC Scopus subject areas

  • Surgery


Dive into the research topics of 'Type I interferons in the treatment of pancreatic cancer: Mechanisms of action and role of related Receptors'. Together they form a unique fingerprint.

Cite this