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Furosemide reverses multidrug resistance status in bladder cancer cells in vitro

Furosemide reverses multidrug resistance status in bladder cancer cells in vitro
Furosemide reverses multidrug resistance status in bladder cancer cells in vitro
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.
0021-9746
912-915
Speers, A.G.
463d8d1b-6bc5-4352-9493-35783dbbe92f
Lwaleed, B.A.
e7c59131-82ad-4a14-a227-7370e91e3f21
Featherstone, J.M.
abbcbcea-0954-43fc-850b-04aba2dba056
Sallis, B.J.
e1e47c7a-8ad4-4ffa-a684-177a240806cc
Cooper, A.J.
8a21c297-eda3-4479-8e81-1de258c8e2a1
Speers, A.G.
463d8d1b-6bc5-4352-9493-35783dbbe92f
Lwaleed, B.A.
e7c59131-82ad-4a14-a227-7370e91e3f21
Featherstone, J.M.
abbcbcea-0954-43fc-850b-04aba2dba056
Sallis, B.J.
e1e47c7a-8ad4-4ffa-a684-177a240806cc
Cooper, A.J.
8a21c297-eda3-4479-8e81-1de258c8e2a1

Speers, A.G., Lwaleed, B.A., Featherstone, J.M., Sallis, B.J. and Cooper, A.J. (2006) Furosemide reverses multidrug resistance status in bladder cancer cells in vitro. Journal of Clinical Pathology, 59 (9), 912-915. (doi:10.1136/jcp.2005.033100). (PMID:16556663)

Record type: Article

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.

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More information

e-pub ahead of print date: 23 March 2006
Published date: September 2006
Organisations: Faculty of Health Sciences

Identifiers

Local EPrints ID: 349258
URI: http://eprints.soton.ac.uk/id/eprint/349258
ISSN: 0021-9746
PURE UUID: d4e7235c-75bb-4023-83dd-afab2123d08e

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Date deposited: 26 Feb 2013 17:00
Last modified: 16 Jul 2019 21:42

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