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

✍ Scribed by Seemann, O. ;Muscheck, M. ;Siegsmund, M. ;Pilch, H. ;Nebe, C. T. ;Rassweiler, J. ;Alken, P.

• Publisher: Springer
• Year: 1995
• Tongue: English
• Weight: 805 KB
• Volume: 22
• Category: Article
• ISSN: 0300-5623
• DOI: 10.1007/bf00296874

✦ Synopsis

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 cross-resistance 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.