Localization of anthracycline accumulation in sensitive and resistant urothelial tumor cell lines.
Emergence of resistance to chemotherapy is a serious clinical problem. Our aim was to investigate anthracycline uptake in sensitive and resistant urothelial cancer cell lines and to manipulate uptake by resistant cells. Anthracyclines exhibit natural fluorescence; therefore, the techniques used for detection were high-resolution fluorescence image analysis and confocal microscopy. Different patterns of intracellular drug distribution were observed in the two cell lines. Sensitive cells showed predominantly nuclear drug localization, while in resistant cells there was nuclear and cytoplasmic fluorescence. Manipulation of drug uptake by resistant cells was achieved using an essential fatty acid, gammalinolenic acid, and the calcium channel blocker, verapamil. Both substances increased drug uptake in resistant cells, with verapamil producing patterns of intracellular drug distribution in resistant cells similar to those of sensitive cells.
Davies
C L
CL
Department of Surgery, University College, London, United Kingdom.
Duffy
P M
PM
MacRobert
A J
AJ
Loizidou
M C
MC
Cooper
A J
AJ
Taylor
I
I
D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000493:pharmacokinetics*; D006801:Humans; D008942:Mitoxantrone / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D015251:Epirubicin; D008942:Mitoxantrone