Establishment and characterization of a multidrug-resistant human bladder carcinoma cell line RT112/D21.
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.
Seemann
O
O
Klinik für Urologie, Städtisches Krankenhaus Heilbronn, Universität Heidelberg, Germany.
Muscheck
M
M
Siegsmund
M
M
Pilch
H
H
Nebe
C T
CT
Rassweiler
J
J
Alken
P
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D002277:Carcinoma / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D006801:Humans; D007150:Immunohistochemistry; D020112:Rhodamine 123; D012235:Rhodamines; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000503:physiopathology*; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012235:Rhodamines; D020112:Rhodamine 123; D004317:Doxorubicin; D014700:Verapamil