CSE1L Silencing Enhances Cytarabine-mediated Cytotoxicity in Acute Myeloid Leukemia

IF 0.9 4区医学

Indian Journal of Hematology and Blood Transfusion Pub Date : 2024-05-27 DOI:10.1007/s12288-024-01773-3

Xiaoyu Liu, Lin Yang, Kunping Guan, Zhen Chen, Hua Yang

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引用次数: 0

Abstract

Purpose

This study aims to investigate the increased toxicity of Cytarabine (Ara-c) by knockdown of chromosome segregation 1-like (CSE1L) in acute myeloid leukemia(AML) cells(Kasumi-1, U937, and THP-1 cells) and to explore its possible mechanisms.

Methods

Target gene silencing was achieved using the shRNA-mediated lentivirus method. Apoptosis was identified using the Annexin V PE/7-AAD double-staining assay. Cell viability was assessed with the Cell Counting Kit-8 (CCK-8) assay. Protein expression was detected by Western blotting.

Results

In vitro, knocking down CSE1L promoted caspase-3 and caspase-9 proteins expression and induced apoptosis in AML cells. Knockdown of CSE1L enhanced AML cells' sensitivity to Ara-c. knockdown of CSE1L reduced the expression levels of p-JKA2 and p-STAT3 proteins, while no significant difference was observed in the expression levels of total JAK2 and STAT3 proteins. Furthermore, JAK2 overexpression reversed the increase in Ara-c toxicity to AML cells caused by CSE1L knockdown.

Conclusion

In conclusion, our study reveals that CSE1L is a potential therapeutic target for overcoming Ara-c resistance in AML cells. Thus, we have gained new insights into the oncogenic process of CSE1L in AML cells and raised the prospect of knockdown of CSE1L in AML in combination with cytarabine-targeted therapy.

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沉默 CSE1L 可增强急性髓性白血病中由阿糖胞苷介导的细胞毒性

目的本研究旨在探讨在急性髓性白血病（AML）细胞（Kasumi-1、U937和THP-1细胞）中敲除染色体分离1样（CSE1L）会增加阿糖胞苷（Ara-c）的毒性，并探讨其可能的机制。采用Annexin V PE/7-AAD双染色法鉴定细胞凋亡。用细胞计数试剂盒-8（CCK-8）检测法评估细胞活力。结果体外敲除 CSE1L 可促进 Caspase-3 和 Caspase-9 蛋白的表达并诱导 AML 细胞凋亡。敲除 CSE1L 会降低 p-JKA2 和 p-STAT3 蛋白的表达水平，而总的 JAK2 和 STAT3 蛋白的表达水平没有明显差异。总之，我们的研究揭示了 CSE1L 是克服 AML 细胞 Ara-c 抗性的潜在治疗靶点。因此，我们对 CSE1L 在 AML 细胞中的致癌过程有了新的认识，并提出了在 AML 中敲除 CSE1L 与细胞抑制剂靶向治疗相结合的前景。

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来源期刊

Indian Journal of Hematology and Blood Transfusion Medicine-Hematology

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期刊介绍： Indian Journal of Hematology and Blood Transfusion is a medium for propagating and exchanging ideas within the medical community. It publishes peer-reviewed articles on a variety of aspects of clinical hematology, laboratory hematology and hemato-oncology. The journal exists to encourage scientific investigation in the study of blood in health and in disease; to promote and foster the exchange and diffusion of knowledge relating to blood and blood-forming tissues; and to provide a forum for discussion of hematological subjects on a national scale. The Journal is the official publication of The Indian Society of Hematology & Blood Transfusion.