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Establishment and characterization of a multidrug-resistant human bladder carcinoma cell line RT112/D21

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Abstract

A doxorubicin-resistant human bladder carcinoma cell line RT112/D21 was established by continuous exposure of the parental line RT112 to increasing concentrations of doxorubicin over a period of 9 months. RT112/D21 cells expressed significantly more P-170 glycoprotein than the parental line, and rhodamine 123 efflux, as a functional parameter of P-170 glycoprotein activity, was increased. RT112/D21 cells were 96 times more resistant to doxorubicin than RT112 cells, and crossresistance to epirubicin and vinblastine was present. Sensitivity to methotrexate and mitomycin C remained unchanged. R-verapamil reversed resistance to doxorubicin, epirubicin and vinblastine in RT112/D21 cells but did not affect sensitivity to methotrexate and mitomycin C. In RT112 cells, R-verapamil had no effect on drug sensitivity. Thus, it may be assumed that primary or induced MDR1 gene-encoded P-170 glycoprotein expression is a relevant mechanism of chemoresistance in transitional cell carcinoma, and that chemotherapeutic strategies in combination with chemosensitizers improve response rates.

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Authors and Affiliations

  1. Klink für Urologie, Städtisches Krankenhaus Heilbronn, Akademisches Lehrkrankenhaus der Universität Heidelberg, Jägerhausstrasse 26, D-74074, Heilbronn, Germany

    O. Seemann

  2. Department of Urology, Faculty of Clinical Medicine, Mannheim Hospital, School of Medicine, University of Heidelberg, Theodor-Kutzer-Ufer, D-68167, Mannheim, Germany

    M. Muscheck, M. Siegsmund, J. Rassweiler & P. Alken

  3. Department of Pathology, Faculty of Clinical Medicine, Mannheim Hospital, School of Medicine, University of Heidelberg, Theodor-Kutzer-Ufer, D-68167, Mannheim, Germany

    H. Pilch

  4. Department of Clinical Chemistry, Faculty of Clinical Medicine, Mannheim Hospital, School of Medicine, University of Heidelberg, Theodor-Kutzer-Ufer, D-68167, Mannheim, Germany

    C. T. Nebe

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  1. O. Seemann
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Seemann, O., Muscheck, M., Siegsmund, M. et al. Establishment and characterization of a multidrug-resistant human bladder carcinoma cell line RT112/D21. Urol. Res. 22, 353–360 (1995). https://doi.org/10.1007/BF00296874

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