Response of pancreatic cancer cells treated with interferon-alpha or beta and co-exposed to ionising radiation.
OBJECTIVE
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.


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.
Jöst
Eva
E
Institute of Toxicology, University Medicine Mainz, Mainz, Germany.
Roos
Wynand P
WP
Kaina
Bernd
B
Schmidberger
Heinz
H
D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
D016898:Interferon-alpha; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; D016899:Interferon-beta