Publikationsdatum:
2017-02-14
Beschreibung:
by 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 jr., 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 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-AS r OXALI 4000 ). SK-N-AS r OXALI 4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-AS r OXALI 4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-AS r OXALI 4000 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-AS r OXALI 4000 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-AS r OXALI 4000 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-AS r OXALI 4000 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.
Digitale ISSN:
1932-6203
Thema:
Medizin
,
Allgemeine Naturwissenschaft
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