Overexpression of SCN5A overcomes ABC transporter-mediated multidrug resistance in acute myeloid leukemia through promoting apoptosis.
Expert Rev Hematol
; 17(1-3): 87-94, 2024.
Article
in En
| MEDLINE
| ID: mdl-38230679
ABSTRACT
BACKGROUND:
This study aimed to explore the effect and mechanism of SCN5A overcoming ATP-binding cassette (ABC) transporter-mediated multidrug resistance (MDR) in acute myeloid leukemia (AML) through promoting apoptosis. RESEARCH DESIGN ANDMETHODS:
The tissues derived from AML patients were divided into Sensitive group and Resistance group according to the presence of drug-resistance. Human AML cell line HL-60 and drug-resistant strain HL-60/ADR were divided into HL-60/ADR-vector group, HL-60/ADR-SCN5A group, HL-60-vector group and HL-60-SCN5A group. RT-qPCR was used to detect the mRNA expression level of SCN5A; MTT assay to assess the survival rate and proliferation level of cells; flow cytometry to determine the apoptosis level; and western blot to check the levels of SCN5A, P-glycoprotein (P-gp), MDR protein 1 (MRP1), MDR gene 1 (MDR1), breast cancer resistance protein (BCRP), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) proteins in cells.RESULTS:
SCN5A expressed lowly in drug-resistant AML tissues and cells. Up-regulation of SCN5A inhibited MDR in HL-60 cells, enhanced the chemosensitivity of HL-60/ADR, and increased the apoptosis levels of HL-60 and HL-60/ADR cells. However, over-expression of SCN5A inhibited the expression of MDR-related proteins.CONCLUSIONS:
SCN5A may overcome ABC transporter-mediated MDR in AML through enhancing the apoptosis and inhibiting the expression of MDR proteins.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Leukemia, Myeloid, Acute
/
ATP-Binding Cassette Transporters
Limits:
Humans
Language:
En
Journal:
Expert Rev Hematol
Journal subject:
HEMATOLOGIA
Year:
2024
Document type:
Article
Affiliation country: