Time-lapse Live Cell Imaging and Flow Analysis of Multidrug Resistance Reversal by Verapamil in Bladder Cancer Cell Lines - 06/08/11
, Alan G. Speers b, c, Matthew C. Hayes a, Brian R. Birch a, Alan J. Cooper a, b
Reprint requests: Bashir A. Lwaleed, B.Sc., Ph.D., F.R.C.Path., Department of Urology, Central Block, Level E, West Wing, Mailpoint 67, Southampton General Hospital, Tremona Road, Southampton SO16 6YD United KingdomRésumé |
Objectives |
To examine the effects of verapamil on the intracellular drug pharmacokinetics of epirubicin using alternative dosing schedules. The results might inform the choices for optimizing clinical chemotherapy.
Methods |
Sensitive parental (MGH-U1) and multidrug resistant (MDR) (MGH-U1R and MGH-U1-MMC) bladder cancer cell lines were used. Fluorescence time-lapsed studies were performed on cells incubated with epirubicin alone or combined with verapamil. Flow cytometry was performed after the alternative dosing regimens.
Results |
Verapamil reversed the epirubicin localization patterns in MDR cells. Time-lapse imaging showed that nuclear epirubicin accumulation in MDR cells with verapamil followed the parental curve. The maximal reversal took >60 minutes. Flow cytometry showed increased epirubicin uptake in MDR cells co-incubated with verapamil. Preincubation was not as effective as co-incubation.
Conclusions |
The results of our model indicate that longer exposure to MDR-class drugs, exemplified by epirubicin, increases uptake and the MDR reversing action of co-treatment with verapamil. The present results highlight the need for additional clinical trials of drug dosing and scheduling for combination intravesical chemotherapy regimens.
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Vol 74 - N° 2
P. 378-384 - août 2009 Retour au numéro
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