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Cisplatin-resistant bladder carcinoma cells: enhanced expression of metallothioneins

Cisplatin is one of the most potent cytotoxic drugs and in chemotherapy has ameliorated numerous tumors. Nevertheless, resistance to cisplatin is a problem that is encountered in the chemotherapy of urologic tumors, especially transitional cell carcinomas. In order to improve definition of the mecha...

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Main Authors: Siegsmund, Michael (Author) , Marx, Claudia Christine (Author) , Seemann, Othmar (Author) , Schummer, Bernhard (Author) , Steidler, Annette (Author) , Toktomambetova, Lira (Author) , Köhrmann, Kai-Uwe (Author) , Rassweiler, Jens (Author) , Alken, Peter (Author)
Format: Article (Journal)
Language:English
Published: June 1999
In: Urological research
Year: 1999, Volume: 27, Issue: 3, Pages: 157-163
ISSN:1434-0879
DOI:10.1007/s002400050103
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s002400050103
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Author Notes:Michael J. Siegsmund, Claudia Marx, Othmar Seemann, Bernhard Schummer, Annette Steidler, Lira Toktomambetova, Kai-Uwe Köhrmann, Jens Rassweiler, Peter Alken
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Summary:Cisplatin is one of the most potent cytotoxic drugs and in chemotherapy has ameliorated numerous tumors. Nevertheless, resistance to cisplatin is a problem that is encountered in the chemotherapy of urologic tumors, especially transitional cell carcinomas. In order to improve definition of the mechanisms of cisplatin-resistance we established a series of cisplatin-resistant sublines from the cell line RT 112 in increasing concentrations of cisplatin. The most resistant subline CP3 is approximately 10 times more resistant than the parental line and shows a 10-fold cross-resistance against methotrexate, whereas vinblastine and doxorubicin are equally effective in the parental and sublines. Combined treatment of CP3 cells with cisplatin and buthionine sulfoximine (BSO) does not result in enhanced cell kill, thereby ruling out glutathione as a resistance mechanism. However, in comparison with parental cells, CP3 cells are about 1.5 times more resistant against cadmium. On the protein level, the cisplatin-resistant cells reveal an enhanced expression of metallothionein II (MTII), but not MTI, suggesting that the cisplatin resistance we observed in these sublines is at least partly mediated by MTII. These sublines will in the future serve as valuable tools for the analysis of cisplatin resistance, especially in view of metallothionein-mediated resistance mechanisms.
Item Description:Gesehen am 04.04.2022
Physical Description:Online Resource
ISSN:1434-0879
DOI:10.1007/s002400050103

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