| Literature DB >> 1353119 |
K Kimiya1, S Naito, T Soejima, N Sakamoto, S Kotoh, J Kumazawa, T Tsuruo.
Abstract
A human bladder cancer cell line resistant to doxorubicin, KK47/ADM has been established in vitro by exposing KK47 parent cells to progressively higher concentrations of the drug over a period of 16 months. The KK47/ADM was 271 times more resistant to doxorubicin than the KK47 parent. The KK47/ADM exhibited cross-resistance to doxorubicin derivatives (pirarubicin, epirubicin), vinca alkaloids (vinblastine, vincristine) and etoposide, but not to cisplatin, carboplatin, mitomycin C, peplomycin and methotrexate. Unlike the KK47 parent, about 70% of the KK47/ADM cells showed a positive reaction with monoclonal antibody against P-glycoprotein, MRK16. Uptake and efflux studies with [14C]doxorubicin indicated that the resistance exhibited by the KK47/ADM line was mainly due to a lower accumulation of the drug caused by an increased active efflux, and these were reversed in the presence of verapamil. Although verapamil enhanced doxorubicin sensitivity of KK47/ADM, a complete overcoming of the resistance could not be obtained. These two lines with different chemosensitivity are thus considered to be a useful model for developing new chemotherapeutic strategies against multidrug resistant bladder cancer.Entities:
Mesh：
Substances：
Year: 1992 PMID： 1353119 DOI： 10.1016/s0022-5347(17)36624-7
Source DB: PubMed Journal: J Urol ISSN： 0022-5347 Impact factor: 7.450