| Title | Time-lapse live cell imaging and flow analysis of multidrug resistance reversal by verapamil in bladder cancer cell lines. | | Author(s) | Featherstone JM, Lwaleed BA, Speers AG, Hayes MC, Birch BR, Cooper AJ | | Institution | Department of Urology, Southampton University Hospitals, National Health Service Trust, United Kingdom. | | Source | Urology 2009 Aug; 74(2):378-84. | | MeSH | Antibiotics, Antineoplastic
Carcinoma, Transitional Cell
Cell Line, Tumor
Cell Nucleus
Cytoplasm
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Epirubicin
Flow Cytometry
Humans
Microscopy, Confocal
Urinary Bladder Neoplasms
Verapamil
| | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19501884 |
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