Fractionated radiation exposure amplifies the radioresistant nature of prostate cancer cells

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作者
N. McDermott
A. Meunier
B. Mooney
G. Nortey
C. Hernandez
S. Hurley
N. Lynam-Lennon
S. H. Barsoom
K. J. Bowman
B. Marples
G. D. D. Jones
L. Marignol
机构
[1] Radiobiology and Molecular Oncology,Department of International Health
[2] Applied Radiation Therapy Trinity,Department Clinical Medicine
[3] Discipline of Radiation Therapy,Department of Surgery
[4] Institute of Molecular Medicine,Department of Cancer Studies & Cancer Research UK Leicester Centre
[5] Trinity College Dublin,Department of Radiation Oncology
[6] Mount Sinai School of Medicine,undefined
[7] Molecular Medicine,undefined
[8] Trinity College Dublin,undefined
[9] Trinity College Dublin,undefined
[10] University of Leicester,undefined
[11] William Beaumont Hospital,undefined
来源
Scientific Reports | / 6卷
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摘要
The risk of recurrence following radiation therapy remains high for a significant number of prostate cancer patients. The development of in vitro isogenic models of radioresistance through exposure to fractionated radiation is an increasingly used approach to investigate the mechanisms of radioresistance in cancer cells and help guide improvements in radiotherapy standards. We treated 22Rv1 prostate cancer cells with fractionated 2 Gy radiation to a cumulative total dose of 60 Gy. This process selected for 22Rv1-cells with increased clonogenic survival following subsequent radiation exposure but increased sensitivity to Docetaxel. This RR-22Rv1 cell line was enriched in S-phase cells, less susceptible to DNA damage, radiation-induced apoptosis and acquired enhanced migration potential, when compared to wild type and aged matched control 22Rv1 cells. The selection of radioresistant cancer cells during fractionated radiation therapy may have implications in the development and administration of future targeted therapy in conjunction with radiation therapy.
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