Saintas 2017 PLOS ONE

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Saintas E, Abrahams L, Ahmad GT, Ajakaiye AM, AlHumaidi AS, Ashmore-Harris C, Clark I, Dura UK, Fixmer CN, Ike-Morris C, Mato Prado M, Mccullough D, Mishra S, Schöler KM, Timur H, Williamson MD, Alatsatianos M, Bahsoun B, Blackburn E, Hogwood CE, Lithgow PE, Rowe M, Yiangou L, Rothweiler F, Cinatl J Jr, Zehner R, Baines AJ, Garrett MD, Gourlay CW, Griffin DK, Gullick WJ, Hargreaves E, Howard MJ, Lloyd DR, Rossman JS, Smales CM, Tsaousis AD, von der Haar T, Wass MN, Michaelis M (2017) 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 12:e0172140.

» PMID: 28192521 Open Access

Saintas E, Abrahams L, Ahmad GT, Ajakaiye AM, AlHumaidi AS, Ashmore-Harris C, Clark I, Dura UK, Fixmer CN, Ike-Morris C, Mato Prado M, Mccullough D, Mishra S, Schöler KM, Timur H, Williamson MD, Alatsatianos M, Bahsoun B, Blackburn E, Hogwood CE, Lithgow PE, Rowe M, Yiangou L, Rothweiler F, Cinatl J Jr, Zehner R, Baines AJ, Garrett MD, Gourlay CW, Griffin DK, Gullick WJ, Hargreaves E, Howard MJ, Lloyd DR, Rossman JS, Smales CM, Tsaousis AD, von der Haar T, Wass MN, Michaelis M (2017) PLOS ONE

Abstract: 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.

Keywords: Human neuroblastoma SK-N-AS cells Bioblast editor: Kandolf G O2k-Network Lab: UK Canterbury Gourlay CW


Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Cancer 

Organism: Human  Tissue;cell: Nervous system, Other cell lines  Preparation: Intact cells 


Coupling state: LEAK, ROUTINE, ET 

HRR: Oxygraph-2k