Type I interferons as radiosensitisers for pancreatic cancer

Abstract

Background: Radiotherapy is an established treatment for malignant localised disease. Pancreatic cancer however seems relatively insensitive to this form of therapy.

Methods: Pancreatic cancer cell lines MiaPaca-2 and Panc-1 were pre-treated with 3000 IU/ml IFNα or 100 IU/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 1000-10.000 IU/ml IFNα or 50-500 IU/ml IFNβ followed by 2Gy irradiation.

Results: The 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 4 Gray). 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 1000 IU/ml (p<0.001) and IFNβ 100 IU/ml (p<0.001) in MiaPaca-2 and with IFNα 5000 IU/ml (p<0.001) and IFNβ 100 IU/ml (p<0.01) in Panc-1. The sensitising enhancement ratio (SER) for IFNα 3000 IU/ml was 2.15 in MiaPaca-2 and 1.90 in Panc-1. For IFNβ 100 IU/ml the SER was 1.72 for in MiaPaca-2 and 1.51 in Panc-1.

Conclusions: Type 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.