Human sulfatase-1 inhibits the migration and proliferation of SMMC-7721 hepatocellular carcinoma cells by downregulating the growth factor signaling
Human sulfatase-1 inhibits the migration and proliferation of SMMC-7721 hepatocellular carcinoma cells by downregulating the growth factor signaling
复制标题
人硫酸酯酶-1通过下调生长因子信号传导抑制 SMMC-7721 肝癌细胞的迁移和增殖
DOI：
10.1111/j.1872-034x.2012.01080.x
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发表时间：
2013-05-01
影响因子：
4.2
通讯作者：
Su, Changqing
中科院分区：
文献类型：
--
作者：
Liu, Hu;Fu, Xiaohui;Su, Changqing
目的：人硫酸酯酶-1 （hSulf-1）基因通过抑制几种生长因子信号通路，调控硫酸肝素蛋白多糖（HSPG）的硫酸化，抑制肿瘤发生和血管生成。由于丝氨酸-苏氨酸蛋白激酶（serine-苏氨酸protein kinase， AKT）和细胞外信号调节激酶（extracellular signal-regulated kinase， ERK）信号通路在细胞存活、增殖、迁移和血管生成中起着至关重要的作用，hSulf-1与肝细胞癌（HCC）细胞中AKT/ERK信号通路的可能相关性有待进一步探讨。方法：构建携带hSulf-1基因的腺病毒Ad5-hSulf1，以及携带hSulf-1 shRNA、AKT shRNA和ERK shRNA的载体，在SMMC-7721细胞中调控hSulf-1、AKT和ERK的表达。采用划伤实验、transwell和3-（4 - 5-二甲基噻唑-2-基）-2 - 5-二苯基溴化四唑检测SMMC-7721细胞的迁移和增殖情况，western blot检测hSulf-1及总AKT和磷酸化AKT、ERK等信号因子的表达。结果：Ad5-hSulf1感染SMMC-7721细胞后，hSulf-1的表达随病毒感染次数的增加而增加。与对照腺病毒Ad5-EGFP和空白对照组相比，Ad5-hSulf1组细胞中AKT和ERK的磷酸化水平降低。同时，细胞迁移和细胞活力明显受到抑制。结论：腺病毒介导的hSulf-1在HCC细胞中的表达可下调AKT和ERK信号通路的活性，抑制HCC细胞的迁移和增殖。hSulf-1基因可作为肿瘤基因治疗的候选抗肿瘤因子。
Aim: The human sulfatase-1 (hSulf-1) gene regulates the sulfation of heparan sulfate proteoglycans (HSPG) and suppresses tumorigenesis and angiogenesis by inhibiting several growth factor signaling pathways. Because the serine-threonine protein kinase (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways are critical in cell survival, proliferation, migration and angiogenesis, the possible correlation between hSulf-1 and AKT/ERK signaling in hepatocellular carcinoma (HCC) cells needs further exploration. Methods: Adenovirus Ad5-hSulf1 carrying the hSulf-1 gene, and vectors carrying hSulf-1 shRNA, AKT shRNA and ERK shRNA were constructed and used to manipulate the expression of hSulf-1, AKT and ERK in SMMC-7721 cells. The scarification test, transwell and 3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide assays were used to examine the cellular migration and proliferation, and the expression of hSulf-1 and signaling factors, including the total and phosphorylated AKT and ERK, was analyzed by western blot in SMMC-7721 cells. Results: After infection with Ad5-hSulf1, the expression of hSulf-1 was increased with viral multiplicity of infection in SMMC-7721 cells. Compared with the control adenovirus Ad5-EGFP and blank control groups, cells in the Ad5-hSulf1 group were showed that the phosphorylation of AKT and ERK was decreased. Meanwhile, the cell migration and cell viability were obviously suppressed. Conclusion: The expression of hSulf-1 mediated by adenovirus in HCC cells could downregulate the activity of AKT and ERK signaling pathways, and inhibit HCC cell migration and proliferation. The hSulf-1 gene may be considered as a candidate of antitumor factor for cancer gene therapy.