Evidence for reduced drug influx in multidrug resistant CEM cells by a fluorescent dye

  • Authors:
    • M Colin
    • C Madoulet
    • H Robichon
    • H Kaplan
    • J Jardillier
  • View Affiliations

  • Published online on: August 1, 1997     https://doi.org/10.3892/ijo.11.2.377
  • Pages: 377-382
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Abstract

Multidrug resistance (MDR) in cancer cells is commonly ascribed to a reduced drug accumulation mediated by an ATP dependent efflux pump. We have developed a new, rapid and quantitative method for measuring influx of BCECF-AM in sensitive (CEM) and MDR cells (CEM/VLB100). The fluorescence of intracellular accumulated BCECF after hydrolysis of BCECF-AM is rapidly visualized by spectrofluorometry. The rate of BCECF-AM entry into CEM/VLB100 cells is considerably lower than that found in CEM cells, similar to 10-fold after 10 min of incubation. This phenomenon is not in relation with a difference of esterase activities, it is not energy or intracellular pH-dependent, and BCECF efflux is negligible. CEM cells exhibited diffuse fluorescence within cytoplasm in contrast with numerous spots of intense labelling, related to the presence of the cytoplasmic vesicles in CEM/VLB100 cells demonstrated by Nomarski's microscopy. MDR modulators such as verapamil, sodium orthovanadate, chlorpromazine or trifluoperazine induce an enhanced influx in CEM/VLB100 cells (150+/-4%; 204+/-17%; 410+/-17% and 229+/-7% respectively) whereas no major differences were noted with the parental sensitive cells. Vinblastine (under conditions close to IC50) increases the influx only in MDR cells (481+/-6%) by a process that is not linked to competitive inhibition of the P170 efflux pump. These results suggest that reduced influx of drugs could be a major defect in MDR cells, a possible role for P170-membrane lipids interactions is discussed.

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August 1997
Volume 11 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Colin M, Madoulet C, Robichon H, Kaplan H and Jardillier J: Evidence for reduced drug influx in multidrug resistant CEM cells by a fluorescent dye. Int J Oncol 11: 377-382, 1997
APA
Colin, M., Madoulet, C., Robichon, H., Kaplan, H., & Jardillier, J. (1997). Evidence for reduced drug influx in multidrug resistant CEM cells by a fluorescent dye. International Journal of Oncology, 11, 377-382. https://doi.org/10.3892/ijo.11.2.377
MLA
Colin, M., Madoulet, C., Robichon, H., Kaplan, H., Jardillier, J."Evidence for reduced drug influx in multidrug resistant CEM cells by a fluorescent dye". International Journal of Oncology 11.2 (1997): 377-382.
Chicago
Colin, M., Madoulet, C., Robichon, H., Kaplan, H., Jardillier, J."Evidence for reduced drug influx in multidrug resistant CEM cells by a fluorescent dye". International Journal of Oncology 11, no. 2 (1997): 377-382. https://doi.org/10.3892/ijo.11.2.377