Dexmedetomidine Promotes Angiogenesis and Vasculogenic Mimicry in Human Hepatocellular Carcinoma through alpha 2-AR/HIF-1 alpha/VEGFA Pathway*

doi:10.3967/bes2022.120

科研成果详情

题名	Dexmedetomidine Promotes Angiogenesis and Vasculogenic Mimicry in Human Hepatocellular Carcinoma through alpha 2-AR/HIF-1 alpha/VEGFA Pathway*
作者	FANG, Tao 1,2; LIN, Li 2; YE, Zhi Jian 2; FANG, Lian2; SHI, Shuai 3; YU, Ke Da 3; MIAO, Hui Hui 1; LI, Tian Zuo 1
发表日期	2022-10
发表期刊	BIOMEDICAL AND ENVIRONMENTAL SCIENCES 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Hepatocellular carcinoma Dexmedetomidine Yohimbine ?2-adrenergic receptor HIF-1a VEGFA Vascular mimicry Angiogenesis
其他关键词	HIF-1-ALPHA ; HYPOXIA
摘要	Objective Dexmedetomidine (DEX), the most specific alpha 2-adrenergic receptor agonist widely used for its sedative and analgesic properties, has been reported to upregulate HIF-1 alpha expression to protect hypoxic and ischemic tissues. However, it is largely unclear whether DEX can also upregulate Hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression and its downstream vascular endothelial growth factor-A (VEGFA) in cancer tissues with oxygen-deficient tumor microenvironment. Methods We used SMMC-7721 cells, MHCC97-H cells, and a mouse model of orthotopic hepatic carcinoma to explore the effect of DEX on angiogenesis and vasculogenic mimicry (VM) and its mechanism. Under normoxic (20% O2) and hypoxic (1% O2) conditions, DEX was used to intervene cells, and yohimbine was used to rescue them. Results The results showed that DEX promoted angiogenesis and VM in human liver cancer cells within a certain dose range, and the addition of yohimbine inhibited this effect. DEX could activate HIF-1 alpha/VEGFA pathway, which was further verified by silencing HIF-1 alpha. Consistently, in vivo results also showed that DEX can up-regulate HIF-1 alpha/VEGFA expression, and enhance the number of VM channels and microvessel density (MVD). Conclusion We believe that HIF-1 alpha/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma, whereas alpha 2-adrenergic receptor mediation might be the critical mechanisms.
资助项目	Natural Science Foundation of Zhejiang Province; Science and Technology Research Program of Jinhua City; [LY19H160002]; [2018-3-001b]; [2017-3-020]
出版者	CHINESE CENTER DISEASE CONTROL & PREVENTION
出版地	BEIJING
ISSN	0895-3988
EISSN	2214-0190
卷号	35 期号:10 页码:931-942
DOI	10.3967/bes2022.120
页数	12
WOS类目	Environmental Sciences ; Public, Environmental & Occupational Health
WOS研究方向	Environmental Sciences & Ecology ; Public, Environmental & Occupational Health
WOS记录号	WOS:000891773100007
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	3644327
SCOPUSEID	2-s2.0-85142828630
通讯作者地址	[LI, Tian Zuo]Department of Anesthesiology,Beijing Shijitan Hospital,Capital Medical University,Beijing,100038,China ; [MIAO, Hui Hui]Department of Anesthesiology,Beijing Shijitan Hospital,Capital Medical University,Beijing,100038,China
Scopus学科分类	Public Health, Environmental and Occupational Health;Health, Toxicology and Mutagenesis
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/172136
专题	附属第一医院_麻醉科温州医科大学
通讯作者	MIAO, Hui Hui; LI, Tian Zuo
作者单位	1.Department of Anesthesiology,Beijing Shijitan Hospital,Capital Medical University,Beijing,100038,China; 2.Department of Anesthesiology,The Affiliated Jinhua Hospital of Wenzhou Medical University,Zhejiang,Jinhua,321000,China; 3.IVF centre,The Affiliated Jinhua Hospital of Wenzhou Medical University,Zhejiang,Jinhua,321000,China
第一作者单位	附属第一医院_麻醉科
推荐引用方式 GB/T 7714	FANG, Tao,LIN, Li,YE, Zhi Jian,et al. Dexmedetomidine Promotes Angiogenesis and Vasculogenic Mimicry in Human Hepatocellular Carcinoma through alpha 2-AR/HIF-1 alpha/VEGFA Pathway*[J]. BIOMEDICAL AND ENVIRONMENTAL SCIENCES,2022,35(10):931-942.
APA	FANG, Tao., LIN, Li., YE, Zhi Jian., FANG, Lian., SHI, Shuai., ... & LI, Tian Zuo. (2022). Dexmedetomidine Promotes Angiogenesis and Vasculogenic Mimicry in Human Hepatocellular Carcinoma through alpha 2-AR/HIF-1 alpha/VEGFA Pathway*. BIOMEDICAL AND ENVIRONMENTAL SCIENCES, 35(10), 931-942.
MLA	FANG, Tao,et al."Dexmedetomidine Promotes Angiogenesis and Vasculogenic Mimicry in Human Hepatocellular Carcinoma through alpha 2-AR/HIF-1 alpha/VEGFA Pathway*".BIOMEDICAL AND ENVIRONMENTAL SCIENCES 35.10(2022):931-942.