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Assessment of multidrug resistance reversal using dielectrophoresis and flow cytometry
Fatima H Labeed1, Helen M Coley, Hilary Thomas
1Centre of Biomedical Engineering, School of Engineering, and Division of Oncology, Postgraduate Medical School, University of Surrey, Guildford, Surrey, United Kingdom.
Abstract:
In cancer, multidrug resistance (MDR) is the simultaneous resistance of tumor cells to different natural product anticancer drugs that have no common structure. This is an impediment to the successful treatment of many human cancers. A common correlate of MDR is the overexpression of a membrane protein, P-glycoprotein. Many studies have shown that MDR can be reversed after the use of substrate analogs, called MDR modulators. However, our understanding of MDR modulation is incomplete. In this article, we examine the electrical properties of the human leukemic cells (K562) and its MDR counterpart (K562AR) using dielectrophoresis and flow cytometry (with a membrane potential sensitive dye, DIOC5), both before and after treatment with XR9576 (a P-glycoprotein-specific MDR-reversal agent). The results show significant differences in the cytoplasmic conductivity between the cell lines themselves, but indicate no significant changes after modulation therapy. We conclude that the process of MDR modulation is not associated with changes in the electrical properties of cancer cells. Moreover, the results demonstrate that using the flow cytometry method alone, with MDR cells, may produce artifactual results--whereas in combination with dielectrophoresis, the results show the role of MDR modulators in preventing drug efflux in MDR cells.
Insights
Multidrug resistance (MDR) in cancer involves tumor cells resisting multiple anticancer drugs. This study found MDR modulation therapy does not alter cancer cell electrical properties, suggesting a new approach for accurate MDR assessment.
Area of Science:
- Biophysics
- Cancer Biology
- Pharmacology
Background:
- Multidrug resistance (MDR) impedes cancer chemotherapy by conferring resistance to structurally diverse anticancer drugs.
- Overexpression of P-glycoprotein is a common hallmark of MDR.
- MDR modulators, such as substrate analogs, are investigated for reversing MDR, but their mechanism remains incompletely understood.
Purpose of the Study:
- To investigate the electrical properties of human leukemic K562 cells and their multidrug-resistant counterpart (K562AR).
- To determine if MDR modulation therapy with XR9576 affects these electrical properties.
- To evaluate the combined use of dielectrophoresis and flow cytometry for assessing MDR modulation.
Main Methods:
- Utilized dielectrophoresis and flow cytometry with the membrane potential-sensitive dye DIOC5.
- Compared electrical properties of K562 and K562AR cells.
- Assessed changes before and after treatment with the P-glycoprotein-specific MDR-reversal agent XR9576.
Main Results:
- Significant differences in cytoplasmic conductivity were observed between K562 and K562AR cell lines.
- No significant changes in electrical properties were detected after MDR modulation therapy.
- Flow cytometry alone may yield artifactual results with MDR cells, whereas its combination with dielectrophoresis clarifies the role of modulators in preventing drug efflux.
Conclusions:
- MDR modulation therapy is not associated with alterations in the electrical properties of cancer cells.
- The combination of dielectrophoresis and flow cytometry provides a more reliable method for evaluating MDR modulation and the function of MDR modulators.
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