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Time-lapse live cell imaging and flow analysis of multidrug resistance reversal by verapamil in bladder cancer cell lines

Time-lapse live cell imaging and flow analysis of multidrug resistance reversal by verapamil in bladder cancer cell lines
Time-lapse live cell imaging and flow analysis of multidrug resistance reversal by verapamil in bladder cancer cell lines
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
0090-4295
378-384
Featherstone, Jonathan M.
bb271404-97a9-4092-bd2d-e4aeb27e6fcc
Lwaleed, Bashir A.
e7c59131-82ad-4a14-a227-7370e91e3f21
Speers, Alan G.
633038d2-91dc-43ba-b910-802dcd64949c
Hayes, Matthew C.
5fc8ef86-8177-4305-ada4-4dd85174ec43
Birch, Brian R.
536ee8d2-9cf9-4412-a29b-d2267fa9d765
Cooper, Alan J.
65dcd1e1-3fcd-46b8-ad5f-f17e0d5b80a5
Featherstone, Jonathan M.
bb271404-97a9-4092-bd2d-e4aeb27e6fcc
Lwaleed, Bashir A.
e7c59131-82ad-4a14-a227-7370e91e3f21
Speers, Alan G.
633038d2-91dc-43ba-b910-802dcd64949c
Hayes, Matthew C.
5fc8ef86-8177-4305-ada4-4dd85174ec43
Birch, Brian R.
536ee8d2-9cf9-4412-a29b-d2267fa9d765
Cooper, Alan J.
65dcd1e1-3fcd-46b8-ad5f-f17e0d5b80a5

Featherstone, Jonathan M., Lwaleed, Bashir A., Speers, Alan G., Hayes, Matthew C., Birch, Brian R. and Cooper, Alan J. (2009) Time-lapse live cell imaging and flow analysis of multidrug resistance reversal by verapamil in bladder cancer cell lines. Urology, 74 (2), 378-384. (doi:10.1016/j.urology.2009.03.012).

Record type: Article

Abstract

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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Published date: August 2009

Identifiers

Local EPrints ID: 73052
URI: http://eprints.soton.ac.uk/id/eprint/73052
ISSN: 0090-4295
PURE UUID: a711acc0-daab-4113-a3ac-c4c55c3ec9ef

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Date deposited: 02 Mar 2010
Last modified: 19 Jul 2019 23:41

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