Non-ionic detergent Tween 80 modulates VP-16 resistance in classical multidrug resistant K562 cells via enhancement of VP-16 influx
| Autor: | Yasushi Sato, Masaaki Hanai, Tetsuo Yamazaki, Ichiro Tsujino, Takashi Horie, Junichiro Mochimaru, Umihiko Sawada |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cancer Research
Polysorbates chemical and pharmacologic phenomena Biology Surface-Active Agents chemistry.chemical_compound hemic and lymphatic diseases medicine Humans Drug Interactions Cell damage Etoposide Cell growth Biological Transport medicine.disease Antineoplastic Agents Phytogenic Molecular biology Drug Resistance Multiple In vitro Oncology chemistry Mechanism of action Biochemistry Cell culture Efflux Growth inhibition medicine.symptom K562 Cells K562 cells |
| Zdroj: | Cancer Letters. 149:153-161 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/s0304-3835(99)00355-9 |
| Popis: | The non-ionic detergent Tween 80, which is used as a solvent for lipophilic drugs such as VP-16 and Taxotere, was found to reverse VP-16 resistance of the P-glycoprotein-associated multidrug resistance phenotype via increasing VP-16 influx. In adriamycin-resistant human chronic myelogenous leukemia K562 cells (K562/ADM), which overexpress mdr1 mRNA, the accumulation of VP-16 was only about 10% that in wild-type K562 cells. Tween 80 enhanced VP-16 accumulation in K562/ADM cells but did not influence VP-16 accumulation in parental K562 cells. VP-16 efflux was rapid and similar in both sensitive and resistant cell lines and was not blocked by Tween 80 or verapamil. Under glucose-free conditions, VP-16 accumulation in K562/ADM cells was only half of that in K562 cells. Tween 80 increased VP-16 accumulation in K562/ADM cells in glucose-free medium. In growth inhibition assay, Tween 80 reversed K562/ADM sensitivity to VP-16 without cell damage. Taken together, Tween 80 reverses VP-16 sensitivity in multidrug -resistant K562 cells by increasing influx, which is considered to be the primary mechanism of VP-16 resistance in K562/ADM cells. |
| Databáze: | OpenAIRE |
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