Activation of DRD5 (dopamine receptor D5) inhibits tumor growth by autophagic cell death

doi:10.1080/15548627.2017.1328347

科研成果详情

题名	Activation of DRD5 (dopamine receptor D5) inhibits tumor growth by autophagic cell death
作者	Leng, Zhi Gen 1,6; Lin, Shao Jian 2; Wu, Ze Rui 1; Guo, Yu Hang 1; Cai, Lin1; Shang, Han Bing 2; Tang, Hao 2; Xue, Ya Jun 3; Lou, Mei Qing 3; Zhao, Wenxiu 5; Le, Wei-Dong 4; Zhao, Wei Guo 2; Zhang, Xun 5; Wu, Zhe Bao 1,2
发表日期	2017-12-31
发表期刊	AUTOPHAGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	autophagic cell death cabergoline dopamine agonist dopamine receptor D5 MTOR prolactinoma reactive oxygen species
其他关键词	UP-REGULATION ; NEUROBLASTOMA-CELLS ; PITUITARY-ADENOMAS ; CANCER-THERAPY ; PROLACTINOMAS ; BROMOCRIPTINE ; DEGRADATION ; ANTAGONIST ; PATHWAY ; STIMULATION
摘要	Dopamine agonists such as bromocriptine and cabergoline have been successfully used in the treatment of pituitary prolactinomas and other neuroendocrine tumors. However, their therapeutic mechanisms are not fully understood. In this study we demonstrated that DRD5 (dopamine receptor D5) agonists were potent inhibitors of pituitary tumor growth. We further found that DRD5 activation increased production of reactive oxygen species (ROS), inhibited the MTOR pathway, induced macroautophagy/autophagy, and led to autophagic cell death (ACD) in vitro and in vivo. In addition, DRD5 protein was highly expressed in the majority of human pituitary adenomas, and treatment of different human pituitary tumor cell cultures with the DRD5 agonist SKF83959 resulted in growth suppression, and the efficacy was correlated with the expression levels of DRD5 in the tumors. Furthermore, we found that DRD5 was expressed in other human cancer cells such as glioblastomas, colon cancer, and gastric cancer. DRD5 activation in these cell lines suppressed their growth, inhibited MTOR activity, and induced autophagy. Finally, in vivo SKF83959 also inhibited human gastric cancer cell growth in nude mice. Our studies revealed novel mechanisms for the tumor suppressive effects of DRD5 agonists, and suggested a potential use of DRD5 agonists as a novel therapeutic approach in the treatment of different human tumors and cancers.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81471392, 81271523]; Zhejiang Open Foundation of the Top Key Discipline [LKYJ015]; Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support [20161407]
出版者	TAYLOR & FRANCIS INC
出版地	PHILADELPHIA
ISSN	1554-8627
EISSN	1554-8635
卷号	13 期号:8 页码:1404-1419
DOI	10.1080/15548627.2017.1328347
页数	16
WOS类目	Cell Biology
WOS研究方向	Cell Biology
WOS记录号	WOS:000409263400010
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	28613975
SCOPUSEID	2-s2.0-85026533921
自科自定义期刊分类	T3(B)类
通讯作者地址	[Wu, Zhe Bao]Department of Neurosurgery,Ruijin Hospital,197 Ruijin Er Road,Shanghai,200025,China
Scopus学科分类	Molecular Biology;Cell Biology
TOP期刊	TOP期刊
引用统计	被引频次：61[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/20027
专题	附属第一医院
通讯作者	Wu, Zhe Bao
作者单位	1.Department of Neurosurgery,First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 2.Department of Neurosurgery,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China; 3.Department of Neurosurgery,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China; 4.Center for Clinical Research on Neurological Diseases,First Affiliated Hospital of Dalian Medical University,Dalian,China; 5.Neuroendocrine Research Laboratory,Massachusetts General Hospital and Harvard Medical School,Boston,United States; 6.Department of Neurosurgery,The People’s Hospital of Yichun City,Yichun,336000,China
第一作者单位	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	Leng, Zhi Gen,Lin, Shao Jian,Wu, Ze Rui,et al. Activation of DRD5 (dopamine receptor D5) inhibits tumor growth by autophagic cell death[J]. AUTOPHAGY,2017,13(8):1404-1419.
APA	Leng, Zhi Gen., Lin, Shao Jian., Wu, Ze Rui., Guo, Yu Hang., Cai, Lin., ... & Wu, Zhe Bao. (2017). Activation of DRD5 (dopamine receptor D5) inhibits tumor growth by autophagic cell death. AUTOPHAGY, 13(8), 1404-1419.
MLA	Leng, Zhi Gen,et al."Activation of DRD5 (dopamine receptor D5) inhibits tumor growth by autophagic cell death".AUTOPHAGY 13.8(2017):1404-1419.