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

发布时间：2019-05-12 17:45

【摘要】：【目的】通过建立肝癌细胞体外缺氧模型分析右美托咪定对缺氧诱导肝癌细胞作用效应的影响及其初步机制的探讨。【方法】人肝癌细胞株MHCC97H、SMCC7721分别使用化学(二氯化钴)及物理(1%O_2)这两种方法来建立缺氧状态下的肝癌细胞体外模型,均培养在含有或者没有100μmol/L的右美托咪定的培养基中。将以上处理的细胞进行细胞增殖实验、单克隆形成实验、小管形成实验来检测右美托咪定对缺氧条件培养的肝癌细胞的增殖能力及血管生成能力的影响,并同时使用western blot检测α2A、HIF-1a及VEGF蛋白的表达情况。【结果】化学方法诱导的肝癌细胞缺氧可以加快肝癌细胞株MHCC97H、SMCC7721的增殖速度(二氯化钴组vs.对照组,MHCC97H和SMCC7721增殖效应分别为:第3天,142.2%和133.8%;第4天,134.7%和131.0%;第5天,133.5%和136.2%,均P0.05),也诱导肝癌细胞的血管生成能力加强。而右美托咪定可抑制缺氧引起的肝癌细胞的增殖效应(联合组vs.二氯化钴组,MHCC97H和SMCC7721增殖效应分别为:第3天,55.7%vs 60.7%;第4天,46.9%vs 58.1%;第5天,46.4%vs 57.0%,均P0.05),减弱肝癌细胞的血管生成能力。而使用物理方法建立的肝癌细胞体外缺氧模型同样得到一致的结果。另外Western blot结果发现右美托咪定可以下调缺氧诱导的肝癌细胞株MHCC97H、SMCC7721的α2A、HIF-1a及VEGF等蛋白的表达。【结论】缺氧可以加快肝癌细胞株MHCC97H、SMCC7721的增殖,同时诱导血管生成能力加强,右美托咪定则可能通过激活α2A肾上腺受体,下调HIF-1a及VEGF蛋白的表达来抑制缺氧诱导的肝癌细胞的作用效应。
[Abstract]:[objective] to establish a hypoxia model of hepatocellular carcinoma cells in vitro to analyze the effect of dexmetomide on hypoxia-induced hepatocellular carcinoma cells and its preliminary mechanism. [methods] Human hepatocellular carcinoma cell line MHCC97H, SMCC7721 used chemical (cobalt dichloride) and physical (1%O_2) methods to establish the in vitro model of HCC cells under hypoxia, and were cultured in the medium containing or without 100 渭 mol / L dexmetomide. The above treated cells were tested for cell proliferation, monoclonal formation and tubule formation to detect the effects of dexmetomide on the proliferation and angiogenic ability of hepatocellular carcinoma cells cultured under anoxic conditions. At the same time, the expression of 伪 2A, HIF 1a and VEGF protein was detected by western blot. [results] hypoxia induced by chemical method could accelerate the proliferation of MHCC97H,SMCC7721 cell line (vs. in cobalt dichloride group). [results] hypoxia induced by chemical method could accelerate the proliferation of HCC cell line. In the control group, the proliferation effects of MHCC97H and SMCC7721 were 142.2% and 133.8% on the 3rd day, 134.7% and 131.0% on the 4th day, respectively. On the 5th day, 133.5% and 136.2%, both P 0.05), also enhanced the angiogenic ability of HCC cells. Dexmetomide can inhibit the proliferation of hepatocellular carcinoma cells induced by hypoxia (combined group vs.) In cobalt dichloride group, the proliferation effects of MHCC97H and SMCC7721 were as follows: 55.7%vs 60.7% on the 3rd day, 46.9%vs 58.1% on the 4th day, respectively. On the 5th day, 46.4%vs 57.0%, all P 0.05), weakened the angiogenic ability of HCC cells. However, the hypoxia model of HCC cells established by physical methods in vitro also obtained the same results. In addition, Western blot results showed that dexmetomide could down-regulate the expression of 伪 2A, HIF-1a and VEGF in MHCC97H,SMCC7721 cell line induced by hypoxia. [conclusion] hypoxia can accelerate the proliferation of hepatocellular carcinoma cell line MHCC97H,SMCC7721. At the same time, the ability of inducing angiogenesis was enhanced. Dexmetomide may inhibit the effect of hypoxia-induced hepatocellular carcinoma cells by activating 伪 2A adrenoceptor and down-regulating the expression of HIF-1a and VEGF proteins.
【作者单位】：华南肿瘤学国家重点实验室//中山大学肿瘤防治中心麻醉科;华南肿瘤学国家重点实验室//中山大学肿瘤防治中心;惠州市中心人民医院;华南肿瘤学国家重点实验室//中山大学肿瘤防治中心肝胆科;
【基金】：国家自然科学基金(30972849)
【分类号】：R614;R735.7

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