Objective Dexmedetomidine (DEX), the most specific α2-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. 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-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 α2-adrenergic receptor mediation might be the critical mechanisms.

FANG Tao;LIN Li;YE Zhi Jian;FANG Lian;SHI Shuai;YU Ke Da;MIAO Hui Hui;LI Tian Zuo

Department of Anesthesiology,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China;Department of Anesthesiology,The Affiliated Jinhua Hospital of Wenzhou Medical University,Jinhua 321000,Zhejiang,China;IVF centre,The Affiliated Jinhua Hospital of Wenzhou Medical University,Jinhua 321000,Zhejiang,China

生物医学与环境科学（英文版）

[1]FANG Tao;LIN Li;YE Zhi Jian;FANG Lian;SHI Shuai;YU Ke Da;MIAO Hui Hui;LI Tian Zuo-.Dexmedetomidine Promotes Angiogenesis and Vasculogenic Mimicry in Human Hepatocellular Carcinoma through α2-AR/HIF-1α/VEGFA Pathway)[J].生物医学与环境科学（英文版）,2022(10):931-942

yohimbine

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