Establishment of doxorubicin-resistant human bladder cancer cell line (BUI-87/ADMR) and its mechanism of multidrug resistance.

To establish a doxorubicin-resistant human bladder cancer cell line, BIU-87/ADMR, and to study its biological characteristics and mechanism of drug resistance.A human bladder cancer cell line resistant to doxorubicin, BIU-87/ADMR, has been established in vitro by exposing BIU-87 parent cells to progressively increasing concentrations of the drug over a period of 8 months. The cell line has been characterized in terms of growth kinetics, morphology, cross-resistance to other anticancerous agents, pharmacokinetics of daunorubicin and expression of P-glycoprotein (P-gp) which is closely related to the MDR phenotype.The BIU-87/ADMR cell line was 6.3 times more resistant to doxorubicin than the parent BIU-87. It exhibited cross-resistance to doxorubicin derivatives (epirubicin, daunorubicin), vincristine and etoposide, but not to cisplatin and mitomycin C. Compared to the parent cells, the resistant cells have a slower growth rate and lower confluent density. Unlike the parent BIU-87, about 75% of the BIU-87/ADMR cells showed a positive reaction with monoclonal antibody against P-gp, JSB-1. Intracellular drug accumulation studies with fluorescence spectrometry indicated that the resistance exhibited by the BIU-87/ ADMR line was mainly caused by an increased active efflux.The results suggest that MDR is an important phenomenon in bladder cancer and that more than one pathway of MDR may be present in human bladder cancer cell lines. BIU-87/ADMR may be a useful model for the development of new chemotherapeutic strategies in overcoming drug-resistance in the treatment of bladder cancer.