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首页> 外文期刊>中国药理学报：英文版 >Effect of 7-hydroxystaurosporine on glioblastoma cell invasion and migration
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Effect of 7-hydroxystaurosporine on glioblastoma cell invasion and migration

机译：7-羟基星形孢菌素对胶质母细胞瘤细胞侵袭和迁移的影响

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摘要

Aim: To investigate the effect of 7-hydroxystaurosporine (UCN-01), a selective protein kinase C (PKC) inhibitor, on cell growth, migration, and invasion in inva sive human glioblastoma U-87MG cells. Methods: PKC activity was determined based on the PKC-catalyzed transfer of the 32p-phosphate group from [g-32p]ATP into a PKC-specific peptide substrate. Cell viability was measured by MTT assay.Cell invasion and migration were evaluated by a Boyden chamber assay and scratch wound assay, respectively. Protein expression was analyzed using Western blot assay. The formation of 3-dimensional cellular aggregates was examined by a cell-cell aggregation assay. Results: UCN-01 treatment resulted in concentration- and time-dependent inhibition of U-87MG cell growth at higher doses (＞ 100 nmol/L), and reduced cell invasion and migration capability at less cytotoxic doses (＜100 nmol/L). UCN-01 significantly repressed PKC activity. Consistent with this result, UCN-01 blocked cell invasion stimulated by phorbel 12-myristate13-acetate (PMA) and ethanol (EtOH), 2 PKC activators. Enforced expression of the tumor suppressor genes BRCA1 and PTEN increased the anti-invasion potential of UCN-01. Exposure to UCN-01 caused a dose-dependent increase in cell adhesion molecule E-cadherin. The effect of UCN-01 on the formation of cell-cell aggregation was significantly reduced by the addition of an anti-E-cadherin antibody. Conclusion: UCN-01 inhibits the invasion and migration of human glioma cells. Accordingly, UCN-01 can have potential clinical applications for the treatment of human glioma metastasis.
机译：目的：研究选择性蛋白激酶C（PKC）抑制剂7-羟基星形孢菌素（UCN-01）对人侵袭性胶质母细胞瘤U-87MG细胞生长，迁移和侵袭的影响。方法：PKC活性是根据PKC催化的32p-磷酸基团从[g-32p] ATP转移到PKC特异性肽底物中而确定的。 MTT法测定细胞活力，Boyden室法和刮伤法分别评价细胞侵袭和迁移。使用蛋白质印迹测定法分析蛋白质表达。通过细胞-细胞聚集测定法检查了三维细胞聚集体的形成。结果：UCN-01处理可在较高剂量（＞ 100 nmol / L）下抑制浓度和时间依赖性的U-87MG细胞生长，并在较低细胞毒性剂量（＜100 nmol / L）下降低细胞的侵袭和迁移能力。 。 UCN-01显着抑制PKC活性。与该结果一致，UCN-01阻断了由phorbel 12-肉豆蔻酸13-乙酸酯（PMA）和乙醇（EtOH）和2种PKC激活剂刺激的细胞侵袭。肿瘤抑制基因BRCA1和PTEN的强制表达增加了UCN-01的抗侵袭能力。暴露于UCN-01会导致细胞粘附分子E-钙粘蛋白的剂量依赖性增加。通过添加抗E-钙粘蛋白抗体，UCN-01对细胞-细胞聚集形成的影响显着降低。结论：UCN-01抑制人胶质瘤细胞的侵袭和迁移。因此，UCN-01在治疗人类神经胶质瘤转移中可能具有潜在的临床应用。

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  • 来源
    《中国药理学报：英文版》 |2005年第4期|492-499|共8页
  • 作者

    Qing-hui MENG; Li-xin ZHOU; Jia-lin LUO; Jian-ping CAO; Jian TONG; Sai-jun FAN;

  • 作者单位

    Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC 20057, USA;

    Institute of Medicine and Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China;

    School of Radiation Medicine and Public Health, Soochow University, Suzhou 215007, China;

    School of Radiation Medicine and Public Health, Soochow University, Suzhou 215007, China;

    School of Radiation Medicine and Public Health, Soochow University, Suzhou 215007, China;

    Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC 20057, USA;

    School of Radiation Medicine and Public Health, Soochow University, Suzhou 215007, China;

  • 收录信息 中国科学引文数据库(CSCD);
  • 原文格式 PDF
  • 正文语种 chi
  • 中图分类
  • 关键词

    7-hydroxystaurosporine; protein kinase C; cell movement: cadherins; BRCA1 protein;

    机译：7-羟基星形孢菌素;蛋白激酶C;细胞运动：钙黏着蛋白;BRCA1蛋白;
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