Determination and reversal of resistance to epirubicin intravesical chemotherapy. A flow cytometric model.
OBJECTIVE
To develop a method of determining the characteristics of epirubicin resistance and to study the reversal of such resistance in the intravesical treatment of superficial bladder cancer, using sensitive and resistant derivatives of a bladder cancer cell line in vitro.


METHODS
Epirubicin fluorescence and flow cytometry were used to measure the intracellular levels of epirubicin in both sensitive and resistant live cultured bladder tumour cells, with and without different doses of the resistance-reversing agent verapamil.


RESULTS
There was a reliable, highly significant and consistent difference in intracellular epirubicin concentration between the resistant and sensitive bladder tumour cells. In addition, it was possible to substantially reverse the features of resistant cell subline with additional verapamil.


CONCLUSIONS
Application of this assay to clinical specimens should allow better targeting of epirubicin intravesical chemotherapy and avoid the premature termination of such treatment in patients whose tumours remain sensitive to this agent. Furthermore, the addition of verapamil to intravesical epirubicin may permit effective treatment of those patients whose tumours have inherent or acquired resistance to epirubicin.
Duffy
P M
PM
Department of Urology, Southampton University Hospitals NHS Trust, Southampton, UK.
Hayes
M C
MC
Cooper
A
A
Smart
C J
CJ
D000283:Administration, Intravesical; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D005453:Fluorescence; D006801:Humans; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D014700:Verapamil