Expression levels of multidrug resistance-associated protein 4 (MRP4) in human leukemia and lymphoma cell lines, and the inhibitory effects of the MRP-specific inhibitor MK-571 on methotrexate distribution in rats
| Autor: | Kenji Takeuchi, Eiji Kashiyama, Masakazu Shibata, Ken Umehara |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
Oncogene business.industry leukemia Cancer lymphoma Spleen Articles General Medicine Pharmacology Cell cycle medicine.disease methotrexate Blood cell medicine.anatomical_structure Immunology and Microbiology (miscellaneous) Apoptosis Cell culture medicine multidrug resistance-associated protein 4 Methotrexate MK-571 business medicine.drug |
| Zdroj: | Experimental and Therapeutic Medicine |
| ISSN: | 1792-1015 1792-0981 |
| DOI: | 10.3892/etm.2012.627 |
| Popis: | In the development of anti-blood cancer drugs, the chronic myelocytic leukemia (KU812), acute myelocytic leukemia (KG-1) and lymphoma (U937) cell lines are commonly used in preclinical pharmacology studies as human cancer xenograft models in mice. In the present study, mRNA expression levels of typical human ATP-binding cassette (ABC) transporters in these human blood cancer cell lines were analyzed by real-time polymerase chain reaction (RT-PCR). Based on the results, the expression level of multidrug resistance-associated protein 4 (MRP4) was found to be extremely high in KU812 cells compared with those of other transporters. Additionally, MRP4 expression levels were found to be relatively high in U937, KG-1 and a blood cell line derived from a healthy subject (RPMI 1788). In addition, to elucidate the contribution of MRP4 to the methotrexate (MTX) distribution in normal blood cells and tissues, [(3)H]MTX was intravenously (i.v.) administered to two groups of rats. Animals in one group received [(3)H]MTX only; the other group was concomitantly administered i.v. MK-571, a typical inhibitor of MRP transporters. No marked difference was observed between the two groups; the Kp values (tissue concentration/plasma concentration) of the concomitant group showed slightly higher values compared with those of the MTX alone group in erythrocytes (1.4 times, P |
| Databáze: | OpenAIRE |
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