Suppression of mTOR pathway and induction of autophagy-dependent cell death by cabergoline

doi:10.18632/oncotarget.5744

科研成果详情

题名	Suppression of mTOR pathway and induction of autophagy-dependent cell death by cabergoline
作者	Lin, Shao Jian 1; Leng, Zhi Gen 2; Guo, Yu Hang 2; Cai, Lin2; Cai, Yu 1; Li, Ning 1; Shang, Han Bing 1; Le, Wei-Dong 3; Zhao, Wei Guo 1; Wu, Zhe Bao 1
发表日期	2015-11-17
发表期刊	ONCOTARGET 影响因子和分区
语种	英语
原始文献类型	Article
关键词	autophagy cabergoline prolactinoma autophagic cell death autophagic flux
其他关键词	DOPAMINE AGONISTS ; PROLACTINOMAS ; DEGRADATION ; BROMOCRIPTINE ; APOPTOSIS ; PROTEINS ; INHIBITION ; GUIDELINES ; RECEPTORS ; RESISTANT
摘要	Cabergoline (CAB), the first-line drug for treatment of prolactinomas, is effective in suppressing prolactin hypersecretion, reducing tumor size, and restoring gonadal function. However, mechanisms for CAB-mediated tumor shrinkage are largely unknown. Here we report a novel cytotoxic mechanism for CAB. CAB induced formation of autophagosome in rat pituitary tumor MMQ and GH3 cells at the early stage through inhibiting mTOR pathway, resulting in higher conversion rates of LC3-I to LC3-II, GFP-LC3 aggregation, and increased autophagosome formation. Interestingly, CAB treatment augmented lysosome acidification and resulted in impaired proteolytic degradation within autolysosomes. This blocked the autophagic flux, leading to the accumulation of p62 aggregation and undigested autolysosomes. Knockdown of ATG7, ATG5, or Becn1, could significantly rescue the CAB-mediated cell death of MMQ cells (p < 0.05). CAB-induced autophagy and blockade of autophagy flux participated in antitumoral action in vivo. In conclusion, our study provides evidence that CAB concomitantly induces autophagy and inhibits the autophagic flux, leading to autophagy-dependent cell death. These findings elucidate novel mechanisms for CAB action.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81271523, 81471392]
出版者	IMPACT JOURNALS LLC
出版地	ORCHARD PARK
ISSN	1949-2553
EISSN	1949-2553
卷号	6 期号:36 页码:39329-39341
DOI	10.18632/oncotarget.5744
页数	13
WOS类目	Oncology ; Cell Biology
WOS研究方向	Oncology ; Cell Biology
WOS记录号	WOS:000366114000067
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	26513171
PMC记录号	PMC4770775
SCOPUSEID	2-s2.0-84948807277
通讯作者地址	[Zhao, Wei Guo]Department of Neurosurgery,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China
Scopus学科分类	Oncology
引用统计	被引频次：31[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/7561
专题	附属第一医院
通讯作者	Zhao, Wei Guo
作者单位	1.Department of Neurosurgery,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China; 2.Department of Neurosurgery,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 3.Institute of Health Sciences,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences-Shanghai Jiao Tong University School of Medicine,Shanghai,200025,China
推荐引用方式 GB/T 7714	Lin, Shao Jian,Leng, Zhi Gen,Guo, Yu Hang,et al. Suppression of mTOR pathway and induction of autophagy-dependent cell death by cabergoline[J]. ONCOTARGET,2015,6(36):39329-39341.
APA	Lin, Shao Jian., Leng, Zhi Gen., Guo, Yu Hang., Cai, Lin., Cai, Yu., ... & Wu, Zhe Bao. (2015). Suppression of mTOR pathway and induction of autophagy-dependent cell death by cabergoline. ONCOTARGET, 6(36), 39329-39341.
MLA	Lin, Shao Jian,et al."Suppression of mTOR pathway and induction of autophagy-dependent cell death by cabergoline".ONCOTARGET 6.36(2015):39329-39341.