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Identification of multi-drug resistant cells in sensitive Friend leukemia cells by quantitative videomicrofluorimetry
1Microfluorimétrie Quantitative et Pharmacocinétique Cellulaire, URA CNRS 1289, Université de Perpignan, Perpignan.
Abstract:
The cellular resistance to cytotoxic drugs, particularly to anthracyclines, remains a major problem in cancer chemotherapy. A number of biochemical mechanisms have been described, one of them being a lower accumulation of drugs in resistant cells. The accumulation of Ho33342 in sensitive and resistant Friend leukemia cells was studied by quantitative fluorescence image analysis, a method which allows investigations to be made on living tissues and cells. The intensity of fluorescence is related to the amount of Ho33342 accumulated into the cells and has been found to be more intense in sensitive cells than in resistant ones. Moreover, the retention of this vital dye was inversely related to the degree of resistance in the three resistant cell lines. The addition of verapamil, which is known to reverse resistance to anthracyclines, resulted in an increase of the amount of Ho33342 accumulated in the resistant cells. Ho33342 presents a higher quantum yield than any other anthracyclines, such as adriamycin and can be used as a microfluorimetric probe to identify the resistant cells in a heterogeneous cell population.
Insights
Cellular drug resistance in cancer chemotherapy is a major challenge. This study shows that sensitive cells accumulate more Ho33342 than resistant cells, and verapamil can reverse this resistance.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Cellular resistance to cytotoxic drugs, especially anthracyclines, hinders effective cancer chemotherapy.
- Reduced drug accumulation in resistant cells is a key mechanism underlying this resistance.
Purpose of the Study:
- To investigate the accumulation of Ho33342 in sensitive and resistant Friend leukemia cells.
- To evaluate Ho33342 as a potential microfluorimetric probe for identifying resistant cancer cells.
Main Methods:
- Quantitative fluorescence image analysis was employed to study Ho33342 accumulation in living cells.
- Verapamil was used to assess its effect on drug accumulation in resistant cell lines.
Main Results:
- Sensitive cells exhibited higher Ho33342 fluorescence intensity, indicating greater drug accumulation, compared to resistant cells.
- Ho33342 retention was inversely correlated with the degree of cellular resistance.
- Verapamil treatment increased Ho33342 accumulation in resistant cells, suggesting reversal of resistance.
Conclusions:
- Ho33342 accumulation is a reliable indicator of cellular sensitivity or resistance to anthracyclines.
- Ho33342 can serve as a microfluorimetric probe for distinguishing resistant cells within heterogeneous populations.
- Understanding drug accumulation mechanisms is crucial for overcoming chemotherapy resistance.