下调ATM/hnRNPK信号降低髓系白血病细胞阿霉素耐药

doi:10.16352/j.issn.1001-6325.2024.12.1638

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (12): 1638-1643.doi: 10.16352/j.issn.1001-6325.2024.12.1638

下调ATM/hnRNPK信号降低髓系白血病细胞阿霉素耐药

张进芳^*, 钟明艳, 杨泉, 冯贝, 李兴东

南方医科大学附属广东省人民医院(广东省医学科学院) 儿童血液科,广东广州 510080

收稿日期:2024-02-28 修回日期:2024-07-08 出版日期:2024-12-05 发布日期:2024-11-26
通讯作者: ^*jinfangzhang1216@126.com
基金资助:
广东省医学科研基金(A2022349)

Down-regulation of ATM/hnRNPK signaling reduces adriamycin resistance of myeloid leukemia

ZHANG Jinfang^*, ZHONG Mingyan, YANG Quan, FENG Bei, LI Xingdong

Department of Paediatric Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510080, China

Received:2024-02-28 Revised:2024-07-08 Online:2024-12-05 Published:2024-11-26
Contact: ^*jinfangzhang1216@126.com

摘要/Abstract

摘要： 目的探索共济失调毛细血管扩张突变蛋白(ATM)/核内不均一的核糖核蛋白K(hnRNPK)信号在调控细胞自噬参与髓系白血病细胞阿霉素耐药中的作用机制。方法用Western blot法检测ATM在阿霉素敏感和耐药细胞株中的表达水平差异。ATM抑制剂及RNA干扰技术抑制ATM在耐药株中的表达水平。在ATM表达调变前后,使用CCK8法检测耐药细胞株对阿霉素药物敏感性,以及使用Western blot法检测人微管相关蛋白轻链3Ⅰ/Ⅱ(LC3Ⅰ/Ⅱ)及hnRNPK的表达水平。结果 ATM在阿霉素耐药细胞株中的表达水平较敏感株明显增高,ATM抑制剂及RNA干扰法降低ATM的表达水平后,耐药株对阿霉素的敏感性可以恢复,且自噬蛋白LC3Ⅱ及hnRNPK的表达与ATM的表达变化一致。结论 ATM/hnRNPK信号异常调控细胞自噬参与髓系白血病细胞阿霉素耐药。

关键词: ATM/hnRNPK, 细胞自噬, 白血病, 阿霉素, 耐药

Abstract: Objective To explore the role of ATM/hnRNPK signaling in the adriamycin resistance of acute myeloid leukemia. Methods Expression of ATM was examined in the adriamycin resistant and sensitive leukemia cell strains with Western blot. ATM expression was down-regulated by RNAi and ATM inhibitor in the adriamycin resistant cell strains. Expression level of hnRNPK and LC3Ⅰ/Ⅱ was detected by Western blot and adriamycin sensitivity was measured by CCK8 assay before and after modulation of ATM expression. Results ATM was overexpressed in adriamycin resistant leukemia cell strains. The decreased expression of ATM restored the sensitivity to adriamycin. Expression level of LC3Ⅱ and hnRNPK was consistent with the modulation of ATM expression. Conclusions The ATM/hnRNPK signaling pathway may play a role in the occurrence of adriamycin resistance in acute myeloid leukemia by regulating autophagy.

Key words: ATM/hnRNPK, autophagy, leukemia, adriamycin, drug resistance

中图分类号:

R733.71

张进芳, 钟明艳, 杨泉, 冯贝, 李兴东. 下调ATM/hnRNPK信号降低髓系白血病细胞阿霉素耐药[J]. 基础医学与临床, 2024, 44(12): 1638-1643.

ZHANG Jinfang, ZHONG Mingyan, YANG Quan, FENG Bei, LI Xingdong. Down-regulation of ATM/hnRNPK signaling reduces adriamycin resistance of myeloid leukemia[J]. Basic & Clinical Medicine, 2024, 44(12): 1638-1643.

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下调ATM/hnRNPK信号降低髓系白血病细胞阿霉素耐药

Down-regulation of ATM/hnRNPK signaling reduces adriamycin resistance of myeloid leukemia

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