Effect of cyclosporin A on daunorubicin accumulation in multidrug-resistant P388 leukemia cells measured by real-time flow cytometry
| Autor: | Kees Nooter, Herman van Dekken, Ger van den Engh, Richard Jonker, Robert Oostrum, Willem Stokdijk |
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| Rok vydání: | 1989 |
| Předmět: |
Cancer Research
Anthracycline Daunorubicin Drug Resistance Radioimmunoassay Cyclosporins Biology Toxicology Flow cytometry Mice Cyclosporin a medicine Tumor Cells Cultured Animals Pharmacology (medical) Drug Interactions Cytotoxicity Chromatography High Pressure Liquid Pharmacology Chromatography Leukemia Experimental medicine.diagnostic_test Dose-Response Relationship Drug Leukemia P388 Lasers Flow Cytometry Molecular biology In vitro Multiple drug resistance Oncology Intracellular medicine.drug |
| Zdroj: | Cancer chemotherapy and pharmacology. 23(5) |
| ISSN: | 0344-5704 |
| Popis: | We investigated the mode of action of cyclosporin A (Cy-A) as a modifier of multidrug resistance in P388 mouse leukemia cells. A fluorescence-activated flow cytometer (FCM) was modified with a flow-through cuvette to allow continuous on-line monitoring of daunorubicin uptake in vitro. The addition of Cy-A to multidrug-resistant P388/R cells at steady-state daunorubicin uptake, led to a dose-dependent increase in cellular daunorubicin accumulation, as measured by FCM and high-performance liquid chromatography (HPLC). A linear relationship was found between the daunorubicin concentration in the incubation medium and the Cy-A concentration required for optimal stimulation of cellular anthracycline accumulation. The results of a cytotoxicity assay indicated that Cy-A completely restored the chemosensitivity of the P388/R cells. Intracellular Cy-A measurements in P388/S and P388/R cells showed that P388/R cells accumulated significantly less Cy-A than P388/S cells. Relatively high daunorubicin concentrations could not restore that accumulation defect. These results suggest that Cy-A promotes cellular anthracycline accumulation by competing for an outward drug-transport system that operates in multidrug-resistant cells. |
| Databáze: | OpenAIRE |
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