Effect of ROCK/Rho-associated kinace inhibitor for malignant gliomas

小GTP结合蛋白Rho及其靶点Rho相关激酶触发细胞内信号级联，控制肌动蛋白细胞骨架，并在细胞运动和粘附中起重要作用。然而，人类胶质瘤的机制仍然知之甚少。本研究的目的是研究Rho-GTP酶在恶性胶质瘤细胞运动和侵袭中的作用，并研究给予ROCK/Rho激酶抑制剂后胶质瘤的活性。我们研究了ROCK/Rho激酶抑制剂Y27632的激活抑制如何影响星形细胞瘤的形态学、侵袭和细胞生长。用ROCK/Rho激酶抑制剂处理胶质瘤细胞导致肌动蛋白细胞骨架重组和改变细胞的形状和分布。我们观察到Rho激酶抑制剂抑制胶质瘤细胞的运动和侵袭，提示ROCK依赖性机制是重要的。结果表明，ROCK/Rho激酶抑制剂可抑制胶质瘤的侵袭和生长，提示ROCK/Rho激酶抑制剂可能具有治疗恶性胶质瘤的潜力。

The small GTP-binding protein Rho and its target Rho-associated kinase trigger an intracellular signaling cascade that controls actin cytoskeleton and plays an important role in cell motility and adhesion. However, the mechanisms in human glliomas remain poorly understood. The purpose of this study was to investigate the role for the Rho-GTPases in cell motility and invasion of malignant gliomas, and to investigate the glioma activity after administration of the ROCK/Rho-kinase inhibitor. We examined how the inhibition of activation of the ROCK/Rho-kinase inhibitor Y27632 affected astrocyotma molphology, invasion and cell growth. Treatment of glioma cells with the ROCK/Rho-kinase inhibitor resulted in actin cytoskeleton reorganization and in the changed shape and distribution of cells. We observed that the Rho-kinase inhibitor inhibited motility and invasion of glioma cells, suggesting the ROCK-dependent mechanism are important. The results indicated that the ROCK/Rho-kinase inhibitor can suppress glioma activity, including invasion and cell growth, suggesting that the ROCK/Rho-kinase inhibitor may have therapeutic potential in the treatment of malignant gliomas.