TY  - JOUR
A1  - Saintas, Emily
A1  - Abrahams, Liam
A1  - Ahmad, Gulshan T.
A1  - Ajakaiye, Anu-Oluwa M.
A1  - AlHumaid, Abdulaziz S. H. A. M.
A1  - Ashmore-Harris, Candice
A1  - Clark, Iain
A1  - Dura, Usha K.
A1  - Fixmer, Carine N.
A1  - Ike-Morris, Chinedu
A1  - Prado, Mireia Mato
A1  - Mccullough, Danielle
A1  - Mishra, Shishir
A1  - Schöler, Katia M. U.
A1  - Timur, Husne
A1  - Williamson, Maxwell D. C.
A1  - Alatsatianos, Markella
A1  - Bahsoun, Basma
A1  - Blackburn, Edith
A1  - Hogwood, Catherine E.
A1  - Lithgow, Pamela E.
A1  - Rowe, Michelle
A1  - Yiangou, Lyto
A1  - Rothweiler, Florian
A1  - Cinatl, Jindrich
A1  - Zehner, Richard
A1  - Baines, Anthony J.
A1  - Garrett, Michelle
A1  - Gourlay, Campbell W.
A1  - Griffin, Darren K.
A1  - Gullick, William J.
A1  - Hargreaves, Emma
A1  - Howard, Mark
A1  - Lloyd, Daniel
A1  - Rossman, Jeremy S.
A1  - Smales, C. Mark
A1  - Tsaousis, Anastasios D.
A1  - Haar, Tobias von der
A1  - Wass, Mark N.
A1  - Michaelis, Martin
T1  - 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
T2  - PLoS one
N2  - 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.
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/41989
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-419896
SN  - 1932-6203
N1  - 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.
VL  - 12
IS  - (2): e0172140
SP  - 1
EP  - 17
PB  - PLoS
CY  - Lawrence, Kan.
ER  -