Establishment and characterization of doxorubicin-resistant human bladder cancer cell line, KK47/ADM

J Urol. 1992 Aug;148(2 Pt 1):441-5. doi: 10.1016/s0022-5347(17)36624-7.

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.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Carcinoma, Transitional Cell / chemistry
  • Carcinoma, Transitional Cell / metabolism
  • Carcinoma, Transitional Cell / pathology*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology*
  • Drug Resistance
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Glycoproteins / analysis
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Tumor Cells, Cultured / drug effects
  • Urinary Bladder Neoplasms / chemistry
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*
  • Verapamil / pharmacology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • Doxorubicin
  • Verapamil