Overexpression of SCN5A overcomes ABC transporter-mediated multidrug resistance in acute myeloid leukemia through promoting apoptosis.

IF 2.3 4区医学 Q2 HEMATOLOGY

Expert Review of Hematology Pub Date : 2024-01-01 Epub Date: 2024-02-02 DOI:10.1080/17474086.2024.2305363

Kun Xu, Xian-Xu Zhuang, Xiao-Wei Shi

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引用次数: 0

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 and methods: 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.

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过表达 SCN5A 可通过促进细胞凋亡克服急性髓性白血病 ABC 转运体介导的多药耐药性。

背景：本研究旨在探讨SCN5A通过促进细胞凋亡克服ATP结合盒（ABC）转运体介导的急性髓性白血病（AML）多药耐药性（MDR）的作用和机制：将急性髓性白血病患者的组织按照是否存在耐药性分为敏感组和耐药组。将人 AML 细胞株 HL-60 和耐药株 HL-60/ADR 分成 HL-60/ADR-vector 组、HL-60/ADR-SCN5A 组、HL-60-vector 组和 HL-60-SCN5A 组。采用 RT-qPCR 法检测 SCN5A 的 mRNA 表达水平；MTT 法评估细胞存活率和增殖水平；流式细胞术检测细胞凋亡水平；和 Western blot 检测细胞中 SCN5A、P-糖蛋白 (P-gp)、MDR 蛋白 1 (MRP1)、MDR 基因 1 (MDR1)、乳腺癌抗性蛋白 (BCRP)、Bcl-2 相关 X 蛋白 (Bax) 和 B 细胞淋巴瘤 2 (Bcl-2) 蛋白的水平。结果显示SCN5A在耐药急性髓细胞性白血病组织和细胞中低表达。上调 SCN5A 可抑制 HL-60 细胞的 MDR，增强 HL-60/ADR 的化疗敏感性，提高 HL-60 和 HL-60/ADR 细胞的凋亡水平。然而，过度表达 SCN5A 会抑制 MDR 相关蛋白的表达：结论：SCN5A可通过增强细胞凋亡和抑制MDR蛋白的表达来克服ABC转运体介导的急性髓细胞白血病MDR。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Hematology HEMATOLOGY-

CiteScore

4.70

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Advanced molecular research techniques have transformed hematology in recent years. With improved understanding of hematologic diseases, we now have the opportunity to research and evaluate new biological therapies, new drugs and drug combinations, new treatment schedules and novel approaches including stem cell transplantation. We can also expect proteomics, molecular genetics and biomarker research to facilitate new diagnostic approaches and the identification of appropriate therapies. Further advances in our knowledge regarding the formation and function of blood cells and blood-forming tissues should ensue, and it will be a major challenge for hematologists to adopt these new paradigms and develop integrated strategies to define the best possible patient care. Expert Review of Hematology (1747-4086) puts these advances in context and explores how they will translate directly into clinical practice.