Suppression of NSCLC progression via the co-administration of Danusertib, an AURK inhibitor, and KRIBB11, an HSF1 inhibitor

doi:10.1016/j.bcp.2024.116155

科研成果详情

题名	Suppression of NSCLC progression via the co-administration of Danusertib, an AURK inhibitor, and KRIBB11, an HSF1 inhibitor
作者	Zhang, Xiang1,2; Lei, Ying 3; Chen, Xiang 4; He, Jiahuang 3; Liu, Zitian1; Zhu, Wentao1; Xu, Yi5; Jin, Xuru3,4
发表日期	2024-05
发表期刊	Biochemical pharmacology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Aurora kinase Danusertib Heat shock factor 1 KRIBB11 Non-small lung cell cancer PI3K/AKT
其他关键词	LUNG-CANCER ; CELL ; FACTOR-1 ; TUMOR
摘要	Aurora kinase (AURK) and heat shock factor 1 (HSF1) are commonly overexpressed in non-small cell lung cancer (NSCLC), correlating with poor prognosis. This study aims to assess the therapeutic potential of combining the Danusertib (Danu, AURK inhibitor) and KRIBB11 (HSF1 inhibitor) for NSCLC treatment. The effects of this combination were investigated in A549 cells and a tumor xenograft mouse model. The findings demonstrate that concurrent administration of Danu and KRIBB11 effectively impedes cell proliferation, induces apoptosis, and triggers G2/M cell cycle arrest. Moreover, the combination treatment upregulates pro-apoptotic proteins (Cleaved-caspase3, Cleaved-PARP, and Bax) while downregulating anti-apoptotic proteins (Bcl-2), as well as G2/M-related proteins (CDC2 and cyclin B1). Additionally, the combination treatment elevates reactive oxygen species (ROS) levels, decreases mitochondrial membrane potential, and activates the DNA damage pathway. Interestingly, we discovered that the PI3K/AKT pathway is involved in mediating the effects of both Danu and KRIBB11. Furthermore, the combination treatment inhibits tumor growth and AKT signaling in the xenograft mouse model, increases levels of the tumor tissue oxidation product malondialdehyde (MDA), and induces DNA damage. To summarize, a potential therapeutic approach for NSCLC may involve dual inhibition of AURK and HSF1, resulting in the downregulation of the PI3K/AKT signaling pathway, and the activation of ROS-mediated mitochondrial and DNA damage pathways.
资助项目	jieping medical foundation[320.6750.2021-02-135];Wenzhou Science and Technology Bureau Medical and Health Project[Y20190443];Competitive Research Projectof Quzhou Science&Technology Bureau[2023k114];Key Laboratory of Interventional Pulmonology of Zhejiang Province[2019E10014];
出版者	PERGAMON-ELSEVIER SCIENCE LTD
ISSN	0006-2952
EISSN	1873-2968
卷号	223
DOI	10.1016/j.bcp.2024.116155
页数	11
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:001219137800001
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	38521474
SCOPUSEID	2-s2.0-85188995160
通讯作者地址	[Xu, Yi]Department of Respiratory and Critical Care Medicine,The First Affiliated Hospital of Wenzhou Medical University,Shangcai Village, wanbaixiang, Ouhai District, Zhejiang Province,Wenzhou City,325000,China
Scopus学科分类	Biochemistry;Pharmacology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/210367
专题	附属第一医院其他_温州医科大学附属衢州医院
通讯作者	Xu, Yi; Jin, Xuru
作者单位	1.Department of Thoracic Surgery,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang Province,Wenzhou,325000,China; 2.Department of Thoracic Surgery,The Quzhou Affiliated Hospital of Wenzhou Medical University,Quzhou People's Hospital,Zhejiang Province,Quzhou,324000,China; 3.Department of Respiratory and Critical Care Medicine,The Quzhou Affiliated Hospital of Wenzhou Medical University,Quzhou People's Hospital,Zhejiang Province,Ouzhou,324000,China; 4.Department of Respiratory and Critical Care Medicine,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang Province,Wenzhou,325000,China; 5.Department of Science & Technology,Department of Urology,The Quzhou Affiliated Hospital of Wenzhou Medical University,Quzhou People's Hospital,Zhejiang Province,Ouzhou,324000,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; 温州医科大学附属衢州医院
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
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Zhang, Xiang,Lei, Ying,Chen, Xiang,et al. Suppression of NSCLC progression via the co-administration of Danusertib, an AURK inhibitor, and KRIBB11, an HSF1 inhibitor[J]. Biochemical pharmacology,2024,223.
APA	Zhang, Xiang., Lei, Ying., Chen, Xiang., He, Jiahuang., Liu, Zitian., ... & Jin, Xuru. (2024). Suppression of NSCLC progression via the co-administration of Danusertib, an AURK inhibitor, and KRIBB11, an HSF1 inhibitor. Biochemical pharmacology, 223.
MLA	Zhang, Xiang,et al."Suppression of NSCLC progression via the co-administration of Danusertib, an AURK inhibitor, and KRIBB11, an HSF1 inhibitor".Biochemical pharmacology 223(2024).