Dexmedetomidine Promotes Angiogenesis and Vasculogenic Mimicry in Human Hepatocellular Carcinoma through α2-AR/HIF-1α/VEGFA Pathway

被引:2
作者
FANG Tao [1 ,2 ]
LIN Li [2 ]
YE Zhi Jian [2 ]
FANG Lian [2 ]
SHI Shuai [3 ]
YU Ke Da [3 ]
MIAO Hui Hui [1 ]
LI Tian Zuo [1 ]
机构
[1] Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University
[2] Department of Anesthesiology, The Affiliated Jinhua Hospital of Wenzhou Medical University  3. IVF centre, The Affiliated Jinhua Hospital of Wenzhou Medical University
关键词
D O I
暂无
中图分类号
R614 [麻醉学]; R735.7 [肝肿瘤];
学科分类号
100214 ; 100217 ;
摘要
Objective Dexmedetomidine(DEX), the most specific α-adrenergic receptor agonist widely used for its sedative and analgesic properties, has been reported to upregulate HIF-1α expression to protect hypoxic and ischemic tissues. However, it is largely unclear whether DEX can also upregulate Hypoxiainducible factor-1 alpha(HIF-1α) 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% O) and hypoxic(1% O) 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-1α/VEGFA pathway, which was further verified by silencing HIF-1α. Consistently, in vivo results also showed that DEX can up-regulate HIF-1α/VEGFA expression, and enhance the number of VM channels and microvessel density(MVD).Conclusion We believe that HIF-1α/VEGFA might be an important signaling pathway by which DEX promotes angiogenesis and VM formation in human hepatocellular carcinoma, whereas α-adrenergic receptor mediation might be the critical mechanisms.
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页码:931 / 942
页数:12
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