Effect of inhibition of the ROCK isoform on RT2 malignant glioma cells.

Effect of inhibition of the ROCK isoform on RT2 malignant glioma cells.
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DOI:
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发表时间:
2010-09
影响因子:
2
通讯作者:
N. Inaba;Sho Ishizawa;M. Kimura;K. Fujioka;Michiko Watanabe;T. Shibasaki;Y. Manome
N. Inaba;Sho Ishizawa;M. Kimura;K. Fujioka;Michiko Watanabe;T. Shibasaki;Y. Manome
中科院分区:
医学4区
文献类型:
--
作者:
N. Inaba;Sho Ishizawa;M. Kimura;K. Fujioka;Michiko Watanabe;T. Shibasaki;Y. Manome

文献摘要

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背景恶性胶质瘤是人体内最难治疗的疾病之一。Rho激酶(ROCK)过度表达,已被认为是该疾病难治性的主要原因。由于需要有效的治疗,因此本研究研究了ROCK亚型抑制的作用。材料与方法将短发夹状RNA转录载体转染大鼠胶质瘤细胞系RT 2,观察细胞特性。还测量了盐酸尼莫司汀(ACNU)抗肿瘤剂对细胞的作用。结果ROCK亚型的抑制不改变细胞生长。细胞周期分析显示ROCK 1下调减少G(0)期细胞数,ROCK 2下调减少G(2)/M期细胞数。当ROCK 1下调的细胞暴露于ACNU时,它们表现出对该试剂的敏感性。结论ROCK 1和ROCK 2在胶质瘤细胞中的作用可能不同。此外,ROCK 1下调和抗肿瘤剂的组合可用于恶性胶质瘤的治疗。
BACKGROUND Malignant glioma is one of the most intractable diseases in the human body. Rho-kinase (ROCK) is overexpressed and has been proposed as the main cause for the refractoriness of the disease. Since efficacious treatment is required, this study investigated the effect of inhibition of ROCK isoforms. MATERIALS AND METHODS The short hairpin RNA transcription vector was transfected into the RT2 rat glioma cell line and the characteristics of the cells were investigated. The effect of nimustine hydrochloride (ACNU) anti-neoplastic agent on cells was also measured. RESULTS Inhibition of ROCK isoforms did not alter cell growth. Cell cycle analysis revealed that ROCK1 down-regulation reduced the G(0) phase population and ROCK2 down-regulation reduced the G(2)/M phase population. When ROCK1-down-regulated cells were exposed to ACNU, they demonstrated susceptibility to the agent. CONCLUSION The roles of ROCK1 and ROCK2 may be different in glioma cells. Furthermore, the combination of ROCK1 down-regulation and an anti-neoplastic agent may be useful for the therapy of malignant glioma.