Imperial College London
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MrPaulRogers

Faculty of Medicine, Department of Infectious Disease

Research Technician
 
 
 
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Contact

 

+44 (0)20 7594 0977paul.rogers CV

 
 
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Location

 

258 Shattock Lab.Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sharp:1995,
author = {Sharp, SY and Rogers, PM and Kelland, LR},
journal = {Clin Cancer Res},
pages = {981--989},
title = {Transport of cisplatin and bis-acetato-ammine-dichlorocyclohexylamine Platinum(IV) (JM216) in human ovarian carcinoma cell lines: identification of a plasma membrane protein associated with cisplatin resistance.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/9816070},
volume = {1},
year = {1995}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The mechanisms by which cis-diamminedichloroplatinum(II) (cisplatin) is transported across the plasma membrane (i.e., passive diffusion versus active transport) were investigated in the 41M and CH1 human ovarian carcinoma cell lines and their acquired cisplatin-resistant variants 41McisR6 and CH1cisR6, respectively. Intracellular cisplatin accumulation was significantly reduced (4.0 +/- 1.7-fold) in the parental 41M line at 4 degrees C when compared to incubations at 37 degrees C. However, no significant differences in platinum uptake were observed in the 41McisR6 and in the CH1 pair of lines at 4 degrees C versus 37 degrees C. Similarly, in the presence of ouabain (an inhibitor of Na+,K+-ATPase), there was a marked reduction (2.0 +/- 0.4-fold) in drug accumulation in the sensitive 41M cells only, and no changes in drug uptake were observed in the other cell lines in the absence or presence of ouabain. Platinum accumulation was significantly enhanced in all cell lines in the presence of metabolic inhibitors (NaF and NaN3). These results suggest that in the parental 41M cell line, cisplatin transport may occur via passive diffusion and active/facilitated transport, whereas in the resistant 41McisR6 variant, cisplatin enters cells by passive diffusion only. The orally active drug bis-acetato-ammine-dichloro-cyclohexylamine platinum(IV) (JM216) is a lipophilic platinum(IV) complex that has been shown to circumvent cisplatin resistance in the 41McisR6 by increasing drug uptake. Across the entire range of concentrations used (5-50 microm), intracellular accumulation of JM216 was significantly reduced in 41M and 41McisR6 cells (3.5 +/- 0.7-fold; P < 0.01), and in CH1 and CH1cisR6 cells (14.2 +/- 6.0-fold; p < 0.01) at 4 degrees C when compared to incubations at 37 degrees C. No significant difference in JM216 uptake was observed in the 41M pair of lines in the absence or presence of ouabain. Additional studies have revealed that the fold reduction observed in cis-am
AU  - Sharp,SY
AU  - Rogers,PM
AU  - Kelland,LR
EP  - 989
PY  - 1995///
SN  - 1078-0432
SP  - 981
TI  - Transport of cisplatin and bis-acetato-ammine-dichlorocyclohexylamine Platinum(IV) (JM216) in human ovarian carcinoma cell lines: identification of a plasma membrane protein associated with cisplatin resistance.
T2  - Clin Cancer Res
UR  - https://www.ncbi.nlm.nih.gov/pubmed/9816070
VL  - 1
ER  -
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