Curcuminoid EF24 enhances the anti-tumour activity of Akt inhibitor MK-2206 through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer

doi:10.1111/bph.13765

科研成果详情

题名	Curcuminoid EF24 enhances the anti-tumour activity of Akt inhibitor MK-2206 through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer
作者	Chen, Xi 1; Dai, Xuanxuan2; Zou, Peng 1; Chen, Weiqian1,3; Rajamanickam, Vinothkumar 1; Feng, Chen 1; Zhuge, Weishan 1; Qiu, Chenyu 1; Ye, Qingqing 1; Zhang, Xiaohua 2; Liang, Guang1
发表日期	2017-05
发表期刊	BRITISH JOURNAL OF PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	PERMEABILITY TRANSITION ; CONCISE GUIDE ; ER STRESS ; INDUCTION ; APOPTOSIS ; CHOP ; PHARMACOLOGY ; CELLS ; CHEMOTHERAPY ; PUBLICATION
摘要	BACKGROUND AND PURPOSE Gastric cancer is one of the leading causes of morbidity and mortality worldwide. Akt is an anti-apoptotic kinase that plays a dynamic role in cell survival and is implicated in the pathogenesis of gastric cancer. MK-2206, the first allosteric inhibitor of Akt, is in clinical trials for a number of cancers. Although preclinical studies showed promise, clinical trials reported it had no effect when given alone at tolerated doses. The aim of our study was to delineate the effects of MK-2206 on gastric cancer cells and explore the ability of combination treatments to enhance the anti-tumour activity of MK-2206. EXPERIMENTAL APPROACH SGC-7901, BGC-823 cells and immunodeficient mice were chosen as a model to study the treatment effects. Changes in cell viability, apoptosis and ROS, endoplasmic reticulum stress and mitochondrial dysfunction in the cells were analysed by MTT assays, ROS imaging and FACSCalibur, electron microscopy, JC-1 staining and western blotting. KEY RESULTS MK-2206 induced apoptotic cell death through the generation of ROS. We utilized ROS production to target gastric cancer cells by combining MK-2206 and an ROS inducer EF24. Our in vitro and in vivo xenograft studies showed that combined treatment with MK-2206 and EF24 synergistically induced apoptosis in gastric cancer cells and caused cell cycle arrest. These activities were mediated through ROS generation and the induction of endoplasmic reticulum stress and mitochondrial dysfunction. CONCLUSION AND IMPLICATIONS Targeting ROS generation by using a combination of an Akt inhibitor and EF24 could have potential as a therapy for gastric cancer.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81503107, 81573657]; Zhejiang Province Natural Science Funding of China [LY13H160022, LY12H16003]; Technology Foundation for Medical Science of Zhejiang Province [2012KYA129]; Wenzhou Science and Technology project [2014Y0344]
出版者	WILEY
出版地	HOBOKEN
ISSN	0007-1188
EISSN	1476-5381
卷号	174 期号:10 页码:1131-1146
DOI	10.1111/bph.13765
页数	16
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000400597900018
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	28255993
PMC记录号	PMC5406301
SCOPUSEID	2-s2.0-85017348791
自科自定义期刊分类	T3(B)类
通讯作者地址	[Zhang, Xiaohua]Department of Surgical Oncology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Pharmacology
引用统计	被引频次：24[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/19357
专题	药学院（分析测试中心）附属第一医院附属第一医院_肿瘤外科药学院（分析测试中心）_生物有机与药物化学研究中心其他_附属第五医院（丽水市中心医院）
通讯作者	Zhang, Xiaohua
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou,325035,China; 2.Department of Surgical Oncology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325035,China; 3.Department of Interventional Radiology,The Fifth Affiliated Hospital of Wenzhou Medical University,Lishui,323000,China
第一作者单位	生物有机与药物化学研究中心
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; 肿瘤外科
第一作者的第一单位	生物有机与药物化学研究中心
推荐引用方式 GB/T 7714	Chen, Xi,Dai, Xuanxuan,Zou, Peng,et al. Curcuminoid EF24 enhances the anti-tumour activity of Akt inhibitor MK-2206 through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer[J]. BRITISH JOURNAL OF PHARMACOLOGY,2017,174(10):1131-1146.
APA	Chen, Xi., Dai, Xuanxuan., Zou, Peng., Chen, Weiqian., Rajamanickam, Vinothkumar., ... & Liang, Guang. (2017). Curcuminoid EF24 enhances the anti-tumour activity of Akt inhibitor MK-2206 through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer. BRITISH JOURNAL OF PHARMACOLOGY, 174(10), 1131-1146.
MLA	Chen, Xi,et al."Curcuminoid EF24 enhances the anti-tumour activity of Akt inhibitor MK-2206 through ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction in gastric cancer".BRITISH JOURNAL OF PHARMACOLOGY 174.10(2017):1131-1146.