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Urological Research

, Volume 22, Issue 6, pp 353–360 | Cite as

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

  • O. Seemann
  • M. Muscheck
  • M. Siegsmund
  • H. Pilch
  • C. T. Nebe
  • J. Rassweiler
  • P. Alken
Original Paper

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.

Key words

Bladder cancer Doxorubicin Multidrug resistance P-170 glycoprotein Rhodamine 123 R-verapamil 

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • O. Seemann
    • 1
  • M. Muscheck
    • 2
  • M. Siegsmund
    • 2
  • H. Pilch
    • 3
  • C. T. Nebe
    • 4
  • J. Rassweiler
    • 2
  • P. Alken
    • 2
  1. 1.Klink für Urologie, Städtisches Krankenhaus HeilbronnAkademisches Lehrkrankenhaus der Universität HeidelbergHeilbronnGermany
  2. 2.Department of Urology, Faculty of Clinical Medicine, Mannheim Hospital, School of MedicineUniversity of HeidelbergMannheimGermany
  3. 3.Department of Pathology, Faculty of Clinical Medicine, Mannheim Hospital, School of MedicineUniversity of HeidelbergMannheimGermany
  4. 4.Department of Clinical Chemistry, Faculty of Clinical Medicine, Mannheim Hospital, School of MedicineUniversity of HeidelbergMannheimGermany

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