Combined inhibition of XIAP and autophagy induces apoptosis and differentiation in acute myeloid leukaemia

doi:10.1111/jcmm.17765

科研成果详情

题名	Combined inhibition of XIAP and autophagy induces apoptosis and differentiation in acute myeloid leukaemia
作者	Huang, Ziyang1,2,3; Zhou, Jifan1,2,3; Jiang, Yinyan1,2,3; Han, Yixiang2,3,4; Wang, Xiaofang1,2,3; Li, Fanfan1,2,3; Jiang, Songfu1,2,3; Yu, Kang1,2,3; Zhang, Shenghui1,2,3,5
发表日期	2023-06
发表期刊	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	acute myeloid leukaemia apoptosis autophagy differentiation XIAP
其他关键词	DOWN-REGULATION ; EXPRESSION ; AML ; DEGRADATION ; CONTRIBUTES ; SURVIVIN ; TARGETS
摘要	Perturbations in autophagy, apoptosis and differentiation have greatly affected the progression and therapy of acute myeloid leukaemia (AML). The role of X-linked inhibitor of apoptosis (XIAP)-related autophagy remains unclear in AML therapeutics. Here, we found that XIAP was highly expressed and associated with poor overall survival in patients with AML. Furthermore, pharmacologic inhibition of XIAP using birinapant or XIAP knockdown via siRNA impaired the proliferation and clonogenic capacity by inducing autophagy and apoptosis in AML cells. Intriguingly, birinapant-induced cell death was aggravated in combination with ATG5 siRNA or an autophagy inhibitor spautin-1, suggesting that autophagy may be a pro-survival signalling. Spautin-1 further enhanced the ROS level and myeloid differentiation in THP-1 cells treated with birinapant. The mechanism analysis showed that XIAP interacted with MDM2 and p53, and XIAP inhibition notably downregulated p53, substantially increased the AMPK alpha 1 phosphorylation and downregulated the mTOR phosphorylation. Combined treatment using birinapant and chloroquine significantly retarded AML progression in both a subcutaneous xenograft model injected with HEL cells and an orthotopic xenograft model injected intravenously with C1498 cells. Collectively, our data suggested that XIAP inhibition can induce autophagy, apoptosis and differentiation, and combined inhibition of XIAP and autophagy may be a promising therapeutic strategy for AML.
资助项目	National Natural Science Foundation of China[82072354];the Health Commission of Zhejiang Province[2020KY179];the Zhejiang Provincial Natural Science Foundation of China[LY20H080005]
出版者	WILEY
ISSN	1582-1838
EISSN	1582-4934
卷号	27 期号:12 页码:1682-1696
DOI	10.1111/jcmm.17765
页数	15
WOS类目	Cell Biology ; Medicine, Research & Experimental
WOS研究方向	Cell Biology ; Research & Experimental Medicine
WOS记录号	WOS:000982609400001
收录类别	SCIE ; PUBMED ; SCOPUS
在线发表日期	2023-05
URL	查看原文
PubMed ID	37154878
SCOPUSEID	2-s2.0-85158106970
通讯作者地址	[Yu, Kang]Department of Hematology,Wenzhou Key Laboratory of Hematology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325015,China ; [Zhang, Shenghui]Laboratory Animal Center,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325015,China
Scopus学科分类	Molecular Medicine;Cell Biology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/180163
专题	附属第一医院第一临床医学院（信息与工程学院）、附属第一医院_中心实验室
通讯作者	Yu, Kang; Zhang, Shenghui
作者单位	1.Department of Hematology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.Institute of Hematology,Wenzhou Medical University,Zhejiang,Wenzhou,China; 3.Wenzhou Key Laboratory of Hematology,Zhejiang,Wenzhou,China; 4.Central Laboratory,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 5.Laboratory Animal Center,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 温州医科大学
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 实验动物中心
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Huang, Ziyang,Zhou, Jifan,Jiang, Yinyan,et al. Combined inhibition of XIAP and autophagy induces apoptosis and differentiation in acute myeloid leukaemia[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2023,27(12):1682-1696.
APA	Huang, Ziyang., Zhou, Jifan., Jiang, Yinyan., Han, Yixiang., Wang, Xiaofang., ... & Zhang, Shenghui. (2023). Combined inhibition of XIAP and autophagy induces apoptosis and differentiation in acute myeloid leukaemia. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 27(12), 1682-1696.
MLA	Huang, Ziyang,et al."Combined inhibition of XIAP and autophagy induces apoptosis and differentiation in acute myeloid leukaemia".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 27.12(2023):1682-1696.