Acquired resistance to oxaliplatin is not directly associated with increased resistance to DNA damage in SK-N-ASrOXALI4000, a newly established oxaliplatin-resistant sub-line of the neuroblastoma cell line SK-N-AS

  • The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-ASrOXALI4000 cells exhibited a stable resistance phenotype that was not affected by culturing the cells for 10 weeks in the absence of oxaliplatin. Interestingly, SK-N-ASrOXALI4000 cells showed no cross resistance to gemcitabine and increased sensitivity to doxorubicin and UVC radiation, alternative treatments that like platinum drugs target DNA integrity. Notably, UVC-induced DNA damage is thought to be predominantly repaired by nucleotide excision repair and nucleotide excision repair has been described as the main oxaliplatin-induced DNA damage repair system. SK-N-ASrOXALI4000 cells were also more sensitive to lysis by influenza A virus, a candidate for oncolytic therapy, than SK-N-AS cells. In conclusion, we introduce a novel oxaliplatin resistance model. The oxaliplatin resistance mechanisms in SK-N-ASrOXALI4000 cells appear to be complex and not to directly depend on enhanced DNA repair capacity. Models of oxaliplatin resistance are of particular relevance since research on platinum drugs has so far predominantly focused on cisplatin and carboplatin.
Metadaten
Author:Emily Saintas, Liam Abrahams, Gulshan T. Ahmad, Anu-Oluwa M. Ajakaiye, Abdulaziz S. H. A. M. AlHumaid, Candice Ashmore-Harris, Iain Clark, Usha K. Dura, Carine N. Fixmer, Chinedu Ike-Morris, Mireia Mato Prado, Danielle Mccullough, Shishir Mishra, Katia M. U. Schöler, Husne Timur, Maxwell D. C. Williamson, Markella Alatsatianos, Basma Bahsoun, Edith Blackburn, Catherine E. Hogwood, Pamela E. Lithgow, Michelle Rowe, Lyto Yiangou, Florian RothweilerGND, Jindrich CinatlORCiDGND, Richard ZehnerORCiDGND, Anthony J. Baines, Michelle Garrett, Campbell W. Gourlay, Darren K. Griffin, William J. Gullick, Emma Hargreaves, Mark Howard, Daniel Lloyd, Jeremy S. Rossman, C. Mark SmalesORCiD, Anastasios D. TsaousisORCiD, Tobias von der Haar, Mark N. WassORCiD, Martin MichaelisORCiDGND
URN:urn:nbn:de:hebis:30:3-419896
DOI:https://doi.org/10.1371/journal.pone.0172140
ISSN:1932-6203
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/28192521
Parent Title (English):PLoS one
Publisher:PLoS
Place of publication:Lawrence, Kan.
Contributor(s):Javier S. Castresana
Document Type:Article
Language:English
Date of Publication (online):2017/02/23
Date of first Publication:2017/02/13
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2017/02/23
Volume:12
Issue:(2): e0172140
Page Number:17
First Page:1
Last Page:17
Note:
Copyright: © 2017 Saintas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS-PPN:448152185
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0