Characterization of a clonal isolate of an oxaliplatin resistant ovarian carcinoma cell line A2780/C10 |
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| Authors: | Hector Suzanne Nava Maria Enriqueta Clark Kimberly Murphy Michael Pendyala Lakshmi |
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| Affiliation: | Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. |
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| Abstract: | ![]()
A single cell clonal sub-line A2780/C10B that is 18-fold resistant to oxaliplatin and approximately threefold cross-resistant to cisplatin and exhibiting a metastasis associated cellular phenotype was characterized for mechanisms of resistance. The cell line exhibited a 50% reduction in the accumulation of both oxaliplatin and cisplatin relative to the parent line, while extensive decline in Pt-DNA adduct levels occurred only following oxaliplatin treatment. The basal GSH levels were fivefold higher in A2780/C10B compared to A2780 and had a fivefold elevation in gamma-GT suggesting this may be the mechanism involved in GSH elevation. The basal levels of ERCC-1, XPA and MRP-2 mRNA levels in A2780/C10B were not higher than those in A2780. The highly reduced Pt-DNA adduct formation only for oxaliplatin, but not cisplatin may be a reflection of the fact that at equimolar concentrations oxaliplatin makes fewer Pt-DNA adducts than cisplatin. The data indicate that multiple lesions occur in a single cell to produce the resistant phenotype. |
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| Keywords: | Oxaliplatin Cisplatin Resistance Platinum EMA" },{" #name" :" keyword" ," $" :{" id" :" cekeyw60" }," $$" :[{" #name" :" text" ," _" :" epithelial membrane antigen EMT" },{" #name" :" keyword" ," $" :{" id" :" cekeyw80" }," $$" :[{" #name" :" text" ," _" :" epithelial to mesenchymal transitions ER" },{" #name" :" keyword" ," $" :{" id" :" cekeyw100" }," $$" :[{" #name" :" text" ," _" :" estrogen receptor GSH" },{" #name" :" keyword" ," $" :{" id" :" cekeyw120" }," $$" :[{" #name" :" text" ," _" :" glutathione γ-GT" },{" #name" :" keyword" ," $" :{" id" :" cekeyw140" }," $$" :[{" #name" :" text" ," _" :" gamma-glutamyltransferase γ-GCS" },{" #name" :" keyword" ," $" :{" id" :" cekeyw160" }," $$" :[{" #name" :" text" ," _" :" gamma-glutamylcysteine synthetase MRP-2" },{" #name" :" keyword" ," $" :{" id" :" cekeyw180" }," $$" :[{" #name" :" text" ," _" :" Multidrug resistance-associated protein 2 NER" },{" #name" :" keyword" ," $" :{" id" :" cekeyw200" }," $$" :[{" #name" :" text" ," _" :" nucleotide excision repair PR" },{" #name" :" keyword" ," $" :{" id" :" cekeyw220" }," $$" :[{" #name" :" text" ," _" :" progesterone receptor Pt" },{" #name" :" keyword" ," $" :{" id" :" cekeyw240" }," $$" :[{" #name" :" text" ," _" :" Platinum SRB" },{" #name" :" keyword" ," $" :{" id" :" cekeyw260" }," $$" :[{" #name" :" text" ," _" :" Sulforhodamine-B |
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