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Time-lapse live cell imaging and flow analysis of multidrug resistance reversal by verapamil in bladder cancer cell lines.
Urology. 2009 Aug; 74(2):378-84.U

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.

Authors+Show Affiliations

Department of Urology, Southampton University Hospitals, National Health Service Trust, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19501884

Citation

Featherstone, Jonathan M., et al. "Time-lapse Live Cell Imaging and Flow Analysis of Multidrug Resistance Reversal By Verapamil in Bladder Cancer Cell Lines." Urology, vol. 74, no. 2, 2009, pp. 378-84.
Featherstone JM, Lwaleed BA, Speers AG, et al. Time-lapse live cell imaging and flow analysis of multidrug resistance reversal by verapamil in bladder cancer cell lines. Urology. 2009;74(2):378-84.
Featherstone, J. M., Lwaleed, B. A., Speers, A. G., Hayes, M. C., Birch, B. R., & Cooper, A. J. (2009). Time-lapse live cell imaging and flow analysis of multidrug resistance reversal by verapamil in bladder cancer cell lines. Urology, 74(2), 378-84. https://doi.org/10.1016/j.urology.2009.03.012
Featherstone JM, et al. Time-lapse Live Cell Imaging and Flow Analysis of Multidrug Resistance Reversal By Verapamil in Bladder Cancer Cell Lines. Urology. 2009;74(2):378-84. PubMed PMID: 19501884.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Time-lapse live cell imaging and flow analysis of multidrug resistance reversal by verapamil in bladder cancer cell lines. AU - Featherstone,Jonathan M, AU - Lwaleed,Bashir A, AU - Speers,Alan G, AU - Hayes,Matthew C, AU - Birch,Brian R, AU - Cooper,Alan J, Y1 - 2009/06/07/ PY - 2008/10/09/received PY - 2009/01/26/revised PY - 2009/03/02/accepted PY - 2009/6/9/entrez PY - 2009/6/9/pubmed PY - 2009/8/19/medline SP - 378 EP - 84 JF - Urology JO - Urology VL - 74 IS - 2 N2 - 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. SN - 1527-9995 UR - https://www.unboundmedicine.com/medline/citation/19501884/Time_lapse_live_cell_imaging_and_flow_analysis_of_multidrug_resistance_reversal_by_verapamil_in_bladder_cancer_cell_lines_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0090-4295(09)00350-1 DB - PRIME DP - Unbound Medicine ER -