Type I interferons as radiosensitisers for pancreatic cancer

被引:19
|
作者
Morak, Marjolein J. M. [1 ]
van Koetsveld, Peter M. [2 ]
Kanaar, Roland [3 ,4 ]
Hofland, Leo J. [2 ]
van Eijck, Casper H. J. [1 ]
机构
[1] Erasmus MC, Dept Surg, NL-3015 CE Rotterdam, Netherlands
[2] Erasmus MC, Dept Internal Med, Div Endocrinol, NL-3015 CE Rotterdam, Netherlands
[3] Erasmus MC, Dept Cell Biol & Genet, Canc Genom Ctr, NL-3015 CE Rotterdam, Netherlands
[4] Erasmus MC, Dept Radiat Oncol, NL-3015 CE Rotterdam, Netherlands
关键词
Pancreatic cancer cell lines; Radiosensitivity; Colony forming assay; Interferon alpha; Interferon beta; RANDOMIZED CONTROLLED-TRIAL; PHASE-III TRIAL; EXTERNAL RADIATION TREATMENT; SQUAMOUS-CELL CARCINOMA; RECOMBINANT INTERFERONS; ADJUVANT RADIOTHERAPY; PERIAMPULLARY REGION; IONIZING-RADIATION; CURATIVE RESECTION; COOPERATIVE GROUP;
D O I
10.1016/j.ejca.2011.03.009
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 IFN alpha or 100 IU/ml IFN beta 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 2 Gy (SF2), cells were pre-treated with 1000-10.000 IU/ml IFN alpha or 50-500 IU/ml IFN beta followed by 2 Gy 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 IFN alpha 1000 IU/ml (p < 0.001) and IFN beta 100 IU/ml (p < 0.001) in MiaPaca-2 and with IFN alpha 5000 IU/ml (p < 0.001) and IFN beta 100 IU/ml (p < 0.01) in Panc-1. The sensitising enhancement ratio (SER) for IFN alpha 3000 IU/ml was 2.15 in MiaPaca-2 and 1.90 in Panc-1. For IFN beta 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 beta is the most promising drug due to its effect in clinically obtainable doses. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1938 / 1945
页数:8
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