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.

PLoS ONE. 2017;12(2):e0172140 DOI 10.1371/journal.pone.0172140

 

Journal Homepage

Journal Title: PLoS ONE

ISSN: 1932-6203 (Online)

Publisher: Public Library of Science (PLoS)

LCC Subject Category: Medicine | Science

Country of publisher: United States

Language of fulltext: English

Full-text formats available: PDF, HTML, XML

 

AUTHORS

Emily Saintas
Liam Abrahams
Gulshan T Ahmad
Anu-Oluwa M Ajakaiye
Abdulaziz S H A M AlHumaidi
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 Rothweiler
Jindrich Cinatl
Richard Zehner
Anthony J Baines
Michelle D Garrett
Campbell W Gourlay
Darren K Griffin
William J Gullick
Emma Hargreaves
Mark J Howard
Daniel R Lloyd
Jeremy S Rossman
C Mark Smales
Anastasios D Tsaousis
Tobias von der Haar
Mark N Wass
Martin Michaelis

EDITORIAL INFORMATION

Peer review

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Instructions for authors

Time From Submission to Publication: 24 weeks

 

Abstract | Full Text

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.