血管生成
血管生成拟态
血管内皮生长因子A
下调和上调
癌症研究
激酶插入结构域受体
血管内皮生长因子
药理学
化学
内分泌学
生物
内科学
医学
癌症
转移
生物化学
基因
血管内皮生长因子受体
作者
Tao Fang,Lin Li,Zhi Jian Ye,Fang Lian,Shuai Shi,Yu Ke,Huihui Miao,Tian Zuo Li
出处
期刊:PubMed
日期:2022-10-20
卷期号:35 (10): 931-942
被引量:3
摘要
Dexmedetomidine (DEX), the most specific α 2-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 Hypoxia-inducible factor-1 alpha (HIF-1α) expression and its downstream vascular endothelial growth factor-A (VEGFA) in cancer tissues with oxygen-deficient tumor microenvironment.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 2) and hypoxic (1% O 2) conditions, DEX was used to intervene cells, and yohimbine was used to rescue them.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).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 2-adrenergic receptor mediation might be the critical mechanisms.
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