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

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-alpha (IFN-alpha), interferon-beta (IFN-beta) 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-alpha is commonly used in the clinic, IFN-beta induced a stronger cytotoxic response than IFN-alpha 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-alpha, it is reasonable to conclude that the sensitising effect of IFN is not mediated through modulating the intrinsic radiosensitivity of pancreatic cancer cells.