Mechanisms of different response to ionizing irradiation in isogenic head and neck cancer cell lines.
Apoptosis
Carcinoma, Squamous Cell
/ metabolism
Cell Cycle
Cell Cycle Proteins
/ metabolism
Cell Line, Tumor
Cell Proliferation
DNA Breaks, Double-Stranded
DNA Repair
DNA-Binding Proteins
/ metabolism
Gene Expression Profiling
Gene Expression Regulation
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms
/ metabolism
Histones
/ metabolism
Humans
Inhibitory Concentration 50
Neoplasm Recurrence, Local
Pharyngeal Neoplasms
/ metabolism
Phenotype
Radiation Tolerance
Radiation, Ionizing
Cancer recurrence
Chemoresistance
DNA damage
DNA repair
Gene expression profiles
Head and neck cancer
Radioresistance
Radiotherapy
Squamous cell carcinoma
Journal
Radiation oncology (London, England)
ISSN: 1748-717X
Titre abrégé: Radiat Oncol
Pays: England
ID NLM: 101265111
Informations de publication
Date de publication:
27 Nov 2019
27 Nov 2019
Historique:
received:
14
06
2019
accepted:
11
11
2019
entrez:
29
11
2019
pubmed:
30
11
2019
medline:
12
5
2020
Statut:
epublish
Résumé
Treatment options for recurrent head and neck tumours in the previously irradiated area are limited, including re-irradiation due to radioresistance of the recurrent tumour and previous dose received by surrounding normal tissues. As an in vitro model to study radioresistance mechanisms, isogenic cells with different radiosensitivity can be used. However, they are not readily available. Therefore, our objective was to establish and characterize radioresistant isogenic human pharyngeal squamous carcinoma cells and to evaluate early radiation response in isogenic parental, radioresistant and radiosensitive cells. Radioresistant cells were derived from parental FaDu cells by repeated exposure to ionizing radiation. Radiosensitivity of the established isogenic radioresistant FaDu-RR cells was evaluated by clonogenic assay and compared to isogenic parental FaDu and radiosensitive 2A3 cells. Additional phenotypic characterization of these isogenic cells with different radiosensitivity included evaluation of chemosensitivity, cell proliferation, cell cycle, radiation-induced apoptosis, resolution of DNA double-strand breaks, and DNA damage and repair signalling gene expression before and after irradiation. In the newly established radioresistant cells in response to 5 Gy irradiation, we observed no alteration in cell cycle regulation, but delayed induction and enhanced resolution of DNA double-strand breaks, lower induction of apoptosis, and pronounced over-expression of DNA damage signalling genes in comparison to parental cells. On the other hand, radiosensitive 2A3 cells were arrested in G We concluded that the emergence of the radioresistance in the established radioresistant isogenic cells can be at least partially attributed to the enhanced DNA double-strand break repair, altered expression of DNA damage signalling and repair genes. On the other hand, in radiosensitive isogenic cells the reduced ability to repair a high number of induced DNA double-strand breaks and no transcriptional response in DNA damage signalling genes indicate on a lack of adaptive response to irradiation. Altogether, our results confirmed that these isogenic cells with different radiosensitivity are an appropriate model to study the mechanisms of radioresistance.
Sections du résumé
BACKGROUND
BACKGROUND
Treatment options for recurrent head and neck tumours in the previously irradiated area are limited, including re-irradiation due to radioresistance of the recurrent tumour and previous dose received by surrounding normal tissues. As an in vitro model to study radioresistance mechanisms, isogenic cells with different radiosensitivity can be used. However, they are not readily available. Therefore, our objective was to establish and characterize radioresistant isogenic human pharyngeal squamous carcinoma cells and to evaluate early radiation response in isogenic parental, radioresistant and radiosensitive cells.
METHODS
METHODS
Radioresistant cells were derived from parental FaDu cells by repeated exposure to ionizing radiation. Radiosensitivity of the established isogenic radioresistant FaDu-RR cells was evaluated by clonogenic assay and compared to isogenic parental FaDu and radiosensitive 2A3 cells. Additional phenotypic characterization of these isogenic cells with different radiosensitivity included evaluation of chemosensitivity, cell proliferation, cell cycle, radiation-induced apoptosis, resolution of DNA double-strand breaks, and DNA damage and repair signalling gene expression before and after irradiation.
RESULTS
RESULTS
In the newly established radioresistant cells in response to 5 Gy irradiation, we observed no alteration in cell cycle regulation, but delayed induction and enhanced resolution of DNA double-strand breaks, lower induction of apoptosis, and pronounced over-expression of DNA damage signalling genes in comparison to parental cells. On the other hand, radiosensitive 2A3 cells were arrested in G
CONCLUSIONS
CONCLUSIONS
We concluded that the emergence of the radioresistance in the established radioresistant isogenic cells can be at least partially attributed to the enhanced DNA double-strand break repair, altered expression of DNA damage signalling and repair genes. On the other hand, in radiosensitive isogenic cells the reduced ability to repair a high number of induced DNA double-strand breaks and no transcriptional response in DNA damage signalling genes indicate on a lack of adaptive response to irradiation. Altogether, our results confirmed that these isogenic cells with different radiosensitivity are an appropriate model to study the mechanisms of radioresistance.
Identifiants
pubmed: 31775835
doi: 10.1186/s13014-019-1418-6
pii: 10.1186/s13014-019-1418-6
pmc: PMC6882348
doi:
Substances chimiques
Cell Cycle Proteins
0
DNA-Binding Proteins
0
GADD45A protein, human
0
H2AX protein, human
0
Histones
0
X-ray repair cross complementing protein 3
0
XRCC2 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
214Subventions
Organisme : Javna Agencija za Raziskovalno Dejavnost RS
ID : P3-0003
Organisme : Javna Agencija za Raziskovalno Dejavnost RS
ID : P3-0307
Organisme : Javna Agencija za Raziskovalno Dejavnost RS
ID : J3-7460
Références
Contemp Oncol (Pozn). 2015;19(4):313-22
pubmed: 26557780
Sci Rep. 2018 Mar 7;8(1):4111
pubmed: 29515153
Carcinogenesis. 2015 Nov;36(11):1397-406
pubmed: 26354779
Nature. 2007 Feb 8;445(7128):671-5
pubmed: 17268471
Cancer Sci. 2015 Dec;106(12):1678-86
pubmed: 26383967
Int J Radiat Biol. 2014 Feb;90(2):115-26
pubmed: 24350914
Radiat Res. 2018 Jun;189(6):644-651
pubmed: 29652621
Clin Cancer Res. 2015 Jul 1;21(13):2898-904
pubmed: 26133775
J Gen Virol. 1999 Jun;80 ( Pt 6):1513-7
pubmed: 10374970
Radiother Oncol. 2011 Oct;101(1):177-82
pubmed: 21700351
Oral Oncol. 1998 Jan;34(1):30-8
pubmed: 9659517
Int J Biochem Cell Biol. 2009 May;41(5):986-9
pubmed: 18760377
Mutat Res Rev Mutat Res. 2015 Oct-Dec;766:1-19
pubmed: 26596544
Radiat Res. 2001 Dec;156(6):739-50
pubmed: 11741498
J Exp Clin Cancer Res. 2009 May 27;28:68
pubmed: 19470182
J Exp Clin Cancer Res. 2012 Feb 08;31:11
pubmed: 22313682
Front Oncol. 2013 May 10;3:113
pubmed: 23675572
Radiat Res. 2005 Jul;164(1):27-35
pubmed: 15966762
Cell Rep. 2018 Dec 18;25(12):3273-3282.e6
pubmed: 30566856
Int J Oral Maxillofac Surg. 2013 Feb;42(2):169-76
pubmed: 23196067
Oral Maxillofac Surg Clin North Am. 2014 May;26(2):123-41
pubmed: 24794262
Radiother Oncol. 2013 May;107(2):242-6
pubmed: 23602369
Anal Quant Cytol Histol. 1993 Aug;15(4):298-302
pubmed: 8397651
Radiother Oncol. 2011 Jul;100(1):33-40
pubmed: 21684027
Biomed Environ Sci. 2008 Aug;21(4):339-44
pubmed: 18837299
Proteomics. 2008 Nov;8(21):4521-33
pubmed: 18821526
Nat Commun. 2016 Feb 15;7:10711
pubmed: 26876487
Int J Mol Sci. 2014 Jan 29;15(2):2157-71
pubmed: 24481064
Oral Oncol. 2014 Jun;50(6):560-4
pubmed: 24134946
Nucleic Acids Res. 2010 Jul;38(Web Server issue):W214-20
pubmed: 20576703
DNA Repair (Amst). 2010 May 4;9(5):517-25
pubmed: 20189471
Radiat Oncol. 2016 Jul 26;11:94
pubmed: 27455841
Int J Radiat Oncol Biol Phys. 2002 Nov 1;54(3):895-902
pubmed: 12377343
Nat Rev Cancer. 2018 Mar;18(3):168-185
pubmed: 29376519
Med Mol Morphol. 2017 Dec;50(4):195-204
pubmed: 29067564
Oncol Lett. 2015 Sep;10(3):1769-1774
pubmed: 26622748
Cancers (Basel). 2017 Dec 28;10(1):null
pubmed: 29283387
Oncotarget. 2016 Jun 14;7(24):35832-35842
pubmed: 27127883
Methods Cell Biol. 1990;33:105-10
pubmed: 1707478
Sci Rep. 2016 Jun 01;6:27043
pubmed: 27245205
Cell Mol Biol Lett. 2012 Jun;17(2):309-22
pubmed: 22396141
Strahlenther Onkol. 2014 Sep;190(9):839-46
pubmed: 24715240
Int J Oncol. 2006 Mar;28(3):705-13
pubmed: 16465376
Head Neck Oncol. 2011 Feb 12;3(1):9
pubmed: 21314983
Sci Rep. 2016 Oct 05;6:34796
pubmed: 27703211
Nat Rev Drug Discov. 2005 Apr;4(4):307-20
pubmed: 15789122
Free Radic Biol Med. 2016 Jun;95:216-29
pubmed: 27012421
Cancer Sci. 2009 Apr;100(4):747-52
pubmed: 19215227
Int J Radiat Biol. 2015;91(12):915-24
pubmed: 26489383
Head Neck. 2015 Jan;37(1):134-50
pubmed: 24481720
Oncol Rep. 2019 Mar;41(3):1658-1668
pubmed: 30628709
Ann Transl Med. 2016 Dec;4(24):524
pubmed: 28149885
Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5057-62
pubmed: 12679524
Cell Death Differ. 2006 Nov;13(11):1915-26
pubmed: 16528386
Nucleic Acids Res. 2018 Jan 4;46(D1):D649-D655
pubmed: 29145629
MBio. 2017 Feb 14;8(1):
pubmed: 28196964
Oral Oncol. 2013 Jun;49(6):560-6
pubmed: 23578372
Int J Radiat Oncol Biol Phys. 2010 Jul 1;77(3):858-66
pubmed: 20510196
Int J Radiat Oncol Biol Phys. 2004 Feb 1;58(2):331-5
pubmed: 14751500
Br J Cancer. 2014 May 27;110(11):2677-87
pubmed: 24786604
Pharmacol Rev. 2012 Jul;64(3):706-21
pubmed: 22659329
Oncotarget. 2015 Oct 27;6(33):34494-509
pubmed: 26460734
Radiat Oncol. 2019 Apr 15;14(1):64
pubmed: 30987655
Int J Cancer. 1997 Sep 26;73(1):164-7
pubmed: 9334825
Int J Radiat Oncol Biol Phys. 2010 Sep 1;78(1):246-56
pubmed: 20615631
Acta Pharmacol Sin. 2011 Feb;32(2):253-8
pubmed: 21293478
Clin Transl Oncol. 2013 Mar;15(3):189-97
pubmed: 22855182
Radiat Res. 2010 Dec;174(6):703-11
pubmed: 21128793
Radiother Oncol. 2009 Jul;92(1):4-14
pubmed: 19446902
Mayo Clin Proc. 2016 Mar;91(3):386-96
pubmed: 26944243
Br J Cancer. 2004 Oct 18;91(8):1543-50
pubmed: 15365572