Response of pancreatic cancer cells treated with interferon-α or β and co-exposed to ionising radiation

Abstract

Purpose: Clinical trials on pancreatic cancer demonstrated that interferons (IFN) improve the therapeutic index of combined radio- and chemotherapy. This is believed to be due to radiosensitisation of cells, which, however, needs experimental verification.

Materials and methods: Here, we compared the survival response of ten pancreatic tumour cell lines following ionising radiation (IR), interferon-α (IFN-α), interferon-β (IFN-β) and combined treatment. The effect of combination treatment on apoptosis induction was also determined.

Results: In most cell lines IFN treatment on its own exerted cytotoxicity, which was independent of the expression level of the IFN receptor on the cell surface. Three cell lines showed a radiosensitisation effect while two showed radioprotection. Although IFN-α is commonly used in the clinic, IFN-β induced a stronger cytotoxic response than IFN-α in vitro. The likely mechanism of enhancement of radiosensitivity in the responsive cell lines was shown to be an increase of the radiation-induced apoptotic response by IFN pretreatment.

Conclusions: Given that the in vitro data do not conform to the impressive clinical results observed after combined radio- and chemotherapy with IFN-α, it is reasonable to conclude that the sensitising effect of IFN is not mediated through modulating the intrinsic radiosensitivity of pancreatic cancer cells.

Keywords:

• interferon-α
• interferon-β
• ionising radiation
• pancreatic cancer
• radiosensitisation and radioprotection

Acknowledgements

Work was supported by a grant of the University of Mainz (MAIFOR) and DFG Ka724 as well as SFB432/B7. We thank Beate Köberle for critical reading of the manuscript.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.