Determination of the relationship between expression and functional activity of multidrug resistance-associated protein 1 using scanning electrochemical microscopy

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  1. Disponible le 21 juillet 2018
  2. Obtenir@CNRC : Determination of the relationship between expression and functional activity of multidrug resistance-associated protein 1 using scanning electrochemical microscopy (Ouvre dans une nouvelle fenêtre)
DOITrouver le DOI : http://doi.org/10.1021/acs.analchem.7b01601
AuteurRechercher : ; Rechercher : ; Rechercher : ; Rechercher : ; Rechercher :
TypeArticle
Titre de la revueAnalytical Chemistry
ISSN0003-2700
1520-6882
Volume89
Numéro17
Pages89888994
RésuméCancer cells can develop multidrug resistance (MDR) after prolonged exposure to chemotherapeutic drugs, which is a severe impediment to successful treatment. MDR is typically associated with transmembrane proteins mediating efflux of administered drugs, thereby keeping their intracellular concentration below the threshold required to kill cells. Although expression assays based on flow cytometry and immunostaining have shown that multidrug resistance-associated protein 1 (MRP1) is prevalent in many cancer types, the functional activity of this efflux pump is more difficult to elucidate, especially at the single-cell level. Herein, we report the measurement of MRP1 functional activity in individual cancer cells using scanning electrochemical microscopy (SECM). Cells were cultured onto plastic substrates containing selective adhesion sites. Optical microscopy and SECM revealed that cells adapt to the underlying surface, while MRP1 functional activity increases once the dimensions of the adhesive islands become smaller than those of the cell itself. Time-lapse SECM imaging revealed a suitable window of 30 min to complete each measurement before the cell undergoes blebbing, which is associated with a considerable increase in functional activity. Distinct cell populations were produced by performing a doxorubicin drug challenge on two parental cell lines (e.g., wild-type HeLa cells and MRP1-overexpressing HeLa-R cells). Expression and functional activity of MRP1 were determined using flow cytometry and SECM, and our findings show that these parameters do not directly correlate. This suggests that functional activity may represent a powerful indicator of a cancer cell’s response to chemotherapeutic treatment and should improve our understanding of efflux mechanisms based on MRP1.
Date de publication
Maison d’éditionAmerican Chemical Society
Langueanglais
AffiliationDispositifs médicaux; Conseil national de recherches Canada
Publications évaluées par des pairsOui
Numéro NPARC23002694
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Identificateur de l’enregistrement8ba6c034-f020-49ef-870a-6513ade854d3
Enregistrement créé2017-12-21
Enregistrement modifié2017-12-21
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