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 pre...
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2017-01-01
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| author | 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 |
| author_facet | 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 |
| author_sort | Emily Saintas |
| collection | DOAJ |
| description | 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. |
| format | Article |
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| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-ef8bcb9439b04f71b952d9ed30ce9beb2025-08-20T02:31:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017214010.1371/journal.pone.0172140Acquired 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.Emily SaintasLiam AbrahamsGulshan T AhmadAnu-Oluwa M AjakaiyeAbdulaziz S H A M AlHumaidiCandice Ashmore-HarrisIain ClarkUsha K DuraCarine N FixmerChinedu Ike-MorrisMireia Mato PradoDanielle McculloughShishir MishraKatia M U SchölerHusne TimurMaxwell D C WilliamsonMarkella AlatsatianosBasma BahsounEdith BlackburnCatherine E HogwoodPamela E LithgowMichelle RoweLyto YiangouFlorian RothweilerJindrich CinatlRichard ZehnerAnthony J BainesMichelle D GarrettCampbell W GourlayDarren K GriffinWilliam J GullickEmma HargreavesMark J HowardDaniel R LloydJeremy S RossmanC Mark SmalesAnastasios D TsaousisTobias von der HaarMark N WassMartin MichaelisThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0172140&type=printable |
| spellingShingle | 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 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 |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0172140&type=printable |
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