Abstract
The choice of cell lines for multidrug resistance (MDR) modulators screening may affect the results obtained. Screening is most often performed in model systems which employ cell lines derived from haematological malignancies. Cell lines originating from solid tumours are far less popular. In the present work, we aimed to test the usefulness of the drug-sensitive human sarcoma cell line MES-SA, and its multidrug-resistant counterpart MES-SA/Dx5, as a model system for modulators' anti-MDR potency evaluation. Overexpression of P-glycoprotein in the resistant but not in the sensitive cell line was confirmed by flow cytometry and confocal microscopy. Flow cytometry demonstrated that verapamil and trifluoperazine reduced MDR in MES-SA/Dx5 cells as assessed by the rhodamine 123 accumulation test. Both modulators also restored in MES-SA/Dx5 cells the drug accumulation pattern typical for sensitive cells, as judged by confocal microscopy. We conclude that the MES-SA and MES-SA/Dx5 cell line pair constitute a good model for MDR modulators study.
Footnotes
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Abbreviations: PHMs, phenothiazine maleates; MDR, multidrug resistance; TFP, trifluoperazine; P-gp, P-glycoprotein; FCS, fetal calf serum; PBS, phosphate buffered saline; FITC, fluorescein isothiocyanate; FAR, fluorescence activity ratio.
- Received July 23, 2004.
- Revision received December 20, 2004.
- Accepted December 30, 2004.
- Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved