中山大学学报（医学科学版）2017，Vol.38Issue(2)：229-236,8.
右美托咪定对缺氧诱导人肝癌细胞增殖和血管生成的影响
Effect of Dexmedetomidine on Proliferation and Angiogenesis of Human Hepatocellular Carcinoma Cell Cultured in Hypoxia Condition and Possible Mechanism
摘要
Abstract
[Objective]This study was conducted to examine the effects of dexmedetomidine on the proliferation and angiogenesis of MHCC97H and SMCC7721 human hepatocellular carcinoma(HCC)cell lines cultured in hypoxia condition in vitro,and investigated the possible mechanism involved.[Methods]MHCC97H and SMCC7721 human HCC cell lines under hypoxia culture condition were treated with presence or absence of dexmedetomidine(100 μmol/L). Cell viability,colony formation,vasculogenic mimicry(VM) formation were assessed. The effects of dexmedetomidine on α-2A adrenergic receptor(α2A),hypoxia induced factor-1a(HIF-1a),and vascular endothelial growth factor(VEGF)protein expression were evaluated with Western blot analysis.[Results]Cell proliferation assay and colony formation assay indicated that hypoxia obviously promoted the proliferation of MHCC 97H and SMCC7721 cells(CoCl2 group vs corresponding control group,the proliferation rate of MHCC97H and SMCC7721:Day 3,142.2%and 133.8%;Day 4,134.7%and 131.0%;Day 5,133.5%and 136.2%;all P<0.05),and VM formation assay suggested that hypoxia increased angiogenesis of MHCC97H and SMCC7721 cells. Whereas dexmedetomidine significantly inhibited the proliferation(Dex+CoCl2 group vs CoCl2 group,the proliferation rate of MHCC97H and SMCC7721:Day 3,55.7%vs 60.7%;Day 4,46.9%vs 58.1%;Day 5,46.4%vs 57.0%,all P<0.05)and angiogenesis of MHCC97H,SMCC7721 cells induced by hypoxia. Dexmedetomidine may exert these functions by activating α-2A adrenergic receptor,causing an decrease in HIF-1a and VEGF protein,while hypoxia activated HIF-1a and VEGF protein to promote the growth and angiogenesis of cells.[Conclusion]The findings provide evidence that hypoxia could promote the proliferation and angiogenesis of MHCC97H and SMCC7721 cells,while dexmedetomidine might inhibit these effects by down-regulating HIF-1a and VEGF protein expression through activatingα-2A adrenergic receptor.关键词
人肝癌细胞/右美托咪定/缺氧/增殖/血管生成Key words
human hepatocellular carcinoma cell/dexmedetomidine/hypoxia/proliferation/angiogenesis分类
医药卫生引用本文复制引用
陈泳花,陈东泰,潘家浩,严俨,元云飞,曾维安..右美托咪定对缺氧诱导人肝癌细胞增殖和血管生成的影响[J].中山大学学报（医学科学版）,2017,38(2):229-236,8.基金项目
国家自然科学基金(30972849 ) （30972849 ）
