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Furosemide reverses multidrug resistance status in bladder cancer cells in vitro.
J Clin Pathol. 2006 Sep; 59(9):912-5.JC

Abstract

BACKGROUND

Multidrug resistance (MDR) has a potentially serious influence on cancer treatment and should be taken into consideration in the design and application of therapeutic regimens. It is mediated through the activity of cellular pumps.

AIM

To investigate whether furosemide, itself a pump-blocker, reverses MDR in an in vitro model.

MATERIALS AND METHODS

An MDR bladder cancer cell line (MGH-u 1R) and its parental (drug sensitive) clone were exposed to epirubicin and furosemide, with the concentration of one drug fixed and that of the other serially diluted in a 96-well plate format. Both drugs formed the variable component in separate experiments. After a 1-h exposure, the cells were washed and replenished with fresh medium. To examine the toxicity of epirubicin and furosemide separately and in combination, monotetrazolium-based assays were carried out. Intracellular epirubicin distribution was assessed by confocal microscopy as a second index of resistance status after in vitro exposure.

RESULTS

MGH-u 1R cells incubated with furosemide showed distribution of drug similar to that in the parental cells (MGH-u 1 sensitive). Controls (without furosemide) continued to show a resistant pattern of fluorescence. In cytotoxicity assays furosemide appeared substantially non-toxic. Resistant cells in the toxicity titration experiments showed increased resistance to levels of furosemide over 500 mug/ml. Parental cells were made only marginally more sensitive against increased background toxicity.

CONCLUSION

Furosemide is effective in reversing MDR status in bladder cancer cell lines in vitro. It may also have an increment of intrinsic cytotoxicity, but only at higher concentrations. We propose a potential for further investigation of furosemide as an adjunct to chemotherapy for superficial bladder cancer.

Authors+Show Affiliations

Department of Biomedical Sciences, University of Portsmouth, Portsmouth, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16556663

Citation

Speers, A G., et al. "Furosemide Reverses Multidrug Resistance Status in Bladder Cancer Cells in Vitro." Journal of Clinical Pathology, vol. 59, no. 9, 2006, pp. 912-5.
Speers AG, Lwaleed BA, Featherstone JM, et al. Furosemide reverses multidrug resistance status in bladder cancer cells in vitro. J Clin Pathol. 2006;59(9):912-5.
Speers, A. G., Lwaleed, B. A., Featherstone, J. M., Sallis, B. J., & Cooper, A. J. (2006). Furosemide reverses multidrug resistance status in bladder cancer cells in vitro. Journal of Clinical Pathology, 59(9), 912-5.
Speers AG, et al. Furosemide Reverses Multidrug Resistance Status in Bladder Cancer Cells in Vitro. J Clin Pathol. 2006;59(9):912-5. PubMed PMID: 16556663.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Furosemide reverses multidrug resistance status in bladder cancer cells in vitro. AU - Speers,A G, AU - Lwaleed,B A, AU - Featherstone,J M, AU - Sallis,B J, AU - Cooper,A J, Y1 - 2006/03/23/ PY - 2006/3/25/pubmed PY - 2006/11/15/medline PY - 2006/3/25/entrez SP - 912 EP - 5 JF - Journal of clinical pathology JO - J Clin Pathol VL - 59 IS - 9 N2 - BACKGROUND: Multidrug resistance (MDR) has a potentially serious influence on cancer treatment and should be taken into consideration in the design and application of therapeutic regimens. It is mediated through the activity of cellular pumps. AIM: To investigate whether furosemide, itself a pump-blocker, reverses MDR in an in vitro model. MATERIALS AND METHODS: An MDR bladder cancer cell line (MGH-u 1R) and its parental (drug sensitive) clone were exposed to epirubicin and furosemide, with the concentration of one drug fixed and that of the other serially diluted in a 96-well plate format. Both drugs formed the variable component in separate experiments. After a 1-h exposure, the cells were washed and replenished with fresh medium. To examine the toxicity of epirubicin and furosemide separately and in combination, monotetrazolium-based assays were carried out. Intracellular epirubicin distribution was assessed by confocal microscopy as a second index of resistance status after in vitro exposure. RESULTS: MGH-u 1R cells incubated with furosemide showed distribution of drug similar to that in the parental cells (MGH-u 1 sensitive). Controls (without furosemide) continued to show a resistant pattern of fluorescence. In cytotoxicity assays furosemide appeared substantially non-toxic. Resistant cells in the toxicity titration experiments showed increased resistance to levels of furosemide over 500 mug/ml. Parental cells were made only marginally more sensitive against increased background toxicity. CONCLUSION: Furosemide is effective in reversing MDR status in bladder cancer cell lines in vitro. It may also have an increment of intrinsic cytotoxicity, but only at higher concentrations. We propose a potential for further investigation of furosemide as an adjunct to chemotherapy for superficial bladder cancer. SN - 0021-9746 UR - https://www.unboundmedicine.com/medline/citation/16556663/Furosemide_reverses_multidrug_resistance_status_in_bladder_cancer_cells_in_vitro_ L2 - https://jcp.bmj.com/lookup/pmidlookup?view=long&pmid=16556663 DB - PRIME DP - Unbound Medicine ER -