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Type I interferons as radiosensitisers for pancreatic cancer

By Marjolein J.M. Morak, Peter M. van Koetsveld, Roland Kanaar, Leo J. Hofland and Casper H.J. van Eijck

Abstract

AbstractBackgroundRadiotherapy is an established treatment for malignant localised disease. Pancreatic cancer however seems relatively insensitive to this form of therapy.MethodsPancreatic cancer cell lines MiaPaca-2 and Panc-1 were pre-treated with 3000IU/ml IFNα or 100IU/ml IFNβ followed by 0, 2, 4, or 6 Gray (Gy) irradiation. Colony forming assay was used to assess the effects on cellgrowth. To measure the surviving fraction at the clinically relevant dose of 2Gy (SF2), cells were pre-treated with 1000–10.000IU/ml IFNα or 50–500IU/ml IFNβ followed by 2Gy irradiation.ResultsThe plating efficiency was 49% for MiaPaca-2 and 22% for Panc-1. MiaPaca-2 was more radiosensitive than Panc-1 (surviving fraction of 0.28 versus 0.50 at 4Gray). The SF2 of MiaPaca-2 was 0.77 while the SF2 of Panc-1 was 0.70. The SF2 significantly decreased after pretreatment with IFNα 1000IU/ml (p<0.001) and IFNβ 100IU/ml (p<0.001) in MiaPaca-2 and with IFNα 5000IU/ml (p<0.001) and IFNβ 100IU/ml (p<0.01) in Panc-1. The sensitising enhancement ratio (SER) for IFNα 3000IU/ml was 2.15 in MiaPaca-2 and 1.90 in Panc-1. For IFNβ 100IU/ml the SER was 1.72 for in MiaPaca-2 and 1.51 in Panc-1.ConclusionsType I interferons have radiosensitising effects in pancreatic cancer cell lines. This radiosensitising property might lead to an improved response to treatment in pancreatic cancer. Interferon β is the most promising drug due to its effect in clinically obtainable doses

Publisher: Elsevier Ltd.
Year: 2011
DOI identifier: 10.1016/j.ejca.2011.03.009
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