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  • Title: Establishment of doxorubicin-resistant human bladder cancer cell line (BUI-87/ADMR) and its mechanism of multidrug resistance.
    Author: Guo H, Lu G, Xiong X, Dong J, Liu S.
    Journal: Chin Med J (Engl); 1997 Mar; 110(3):167-72. PubMed ID: 9594332.
    Abstract:
    OBJECTIVE: To establish a doxorubicin-resistant human bladder cancer cell line, BIU-87/ADMR, and to study its biological characteristics and mechanism of drug resistance. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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