Role of drug transporters in the sensitivity of acute myeloid leukemia to sorafenib
[EN]Chemoresistance often limits the success of the pharmacological treatment in acute myeloid leukemia (AML) patients. Although positive results have been obtained with tyrosine kinase inhibitors (TKIs), such as sorafenib, especially in patients with Fms-like tyrosine kinase 3 (FLT3)-positive AML,...
| Autores: | , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universidad de Salamanca (USAL) |
| Repositorio: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/146674 |
| Acceso en línea: | http://hdl.handle.net/10366/146674 |
| Access Level: | acceso abierto |
| Palabra clave: | AML Cancer Chemoresistance Chemotherapy Tyrosine kinase inhibitor Chemotherapy, Cancer, Regional Perfusion Chemoreceptor Cells 3201.01 Oncología 3205.04 Hematología quimioterapia del cáncer por perfusión regional células quimiorreceptoras síntomas de cáncer |
| Sumario: | [EN]Chemoresistance often limits the success of the pharmacological treatment in acute myeloid leukemia (AML) patients. Although positive results have been obtained with tyrosine kinase inhibitors (TKIs), such as sorafenib, especially in patients with Fms-like tyrosine kinase 3 (FLT3)-positive AML, the success of chemotherapy is very heterogeneous.The sensitivity to sorafenib-induced cell death (MTT test and anexin V/7-AAD method) was evaluated in five different cell lines: MOLM-13, OCI-AML2, HL-60, HEL and K-562. The transportome was characterized by measuring mRNA using RT-qPCR. Drug uptake/efflux was determined by flow cytometry using specific substrates and inhibitors. The cytostatic response to sorafenib was: MOLM-13»OCI-AML2>HL- 60>HEL≈K-562. Regarding efflux pumps, MDR1 was highly expressed in HEL>K- 562≈MOLM-13, but not in OCI-AML2 and HL-60. BCRP and MPR3 expression was low in all cell lines, whereas MRP4 and MRP5 expression was from moderate to high. Flow cytometry studies demonstrated that MRP4, but not MRP5, was functional. |
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