Nestin small interfering RNA (siRNA) reduces cell growth in cultured astrocytoma cells
Nestin small interfering RNA (siRNA) reduces cell growth in cultured astrocytoma cells
复制标题
Nestin 小干扰 RNA (siRNA) 减少培养的星形细胞瘤细胞的细胞生长
DOI：
10.1016/j.brainres.2007.11.026
复制
发表时间：
2008-02-27
期刊：
影响因子：
2.9
通讯作者：
Chan, Ying-Shing
中科院分区：
文献类型：
--
作者：
Wei, Li-Chun;Shi, Mei;Chan, Ying-Shing
巢蛋白是在发育中的中枢神经系统（CNS）的神经干/祖细胞中短暂表达的胚胎中间丝。越来越多的证据表明，nestin在各种中枢神经系统损伤的病理性胶质源性肿瘤细胞和反应性星形胶质细胞中也大量表达，这表明nestin可能在星形胶质细胞源性肿瘤细胞的生长或增殖中起着至关重要的作用。本研究采用新型小干扰RNA （siRNA）方法对大鼠星形细胞瘤C6细胞株进行细胞培养，探讨巢蛋白表达在CNS肿瘤细胞生长或存活中的可能作用。细胞转染nestin siRNA双链6 h，维持细胞培养48 h后，检测培养的星形细胞瘤细胞nestin的表达和细胞生长情况，发现nestin siRNA对培养的星形细胞瘤细胞生长有有效的抑制作用，且呈剂量依赖性。定量数据分析显示，30 ~ 120 nM的nestin siRNA剂量显著降低了细胞数量和nestin mRNA和蛋白的表达水平。巢蛋白siRNA还能抑制细胞胶质原纤维酸蛋白的表达，但对细胞增殖标志物Ki-67蛋白的表达水平无明显影响。本研究提供的体外证据表明，nestin siRNA可以有效阻断nestin的表达，降低培养的C6星形胶质细胞瘤细胞的生长，强烈提示nestin siRNA诱导的抑制肿瘤细胞生长可能为治疗CNS星形胶质细胞瘤事件提供潜在的新的临床治疗方法。(C) 2007 Elsevier B.V.版权所有
Nestin is an embryonic intermediate filament that transiently expressed in the neural stem/progenitor cells in the developing central nervous system (CNS). Growing evidence has shown that abundant expression of nestin also occurs in both pathological glial-derived tumor cells and reactive astrocytes in various CNS injuries, implying that nestin may play a crucial role in cell growth or proliferation of astrocyte-derived tumor cells. In the present study, we have investigated the possible role of nestin expression in cell growth or survival of CNS tumor cells by using novel small interfering RNA (siRNA) method in cell culture of rat astrocytoma C6 cell line. The nestin expression and cell growth of the cultured astrocytoma cells were examined after nestin siRNA duplex was delivered by cell transfection for 6 h and cell culture was maintained for 48 h. It revealed an effective suppression influence of nestin siRNA on cell growth of cultured astrocytoma cells in a dose-dependent manner. Quantitative data analysis showed that the doses of nestin siRNA at 30-120 nM significantly decreased both cell numbers and expression levels of nestin mRNA and protein. The nestin siRNA also suppressed expression of cellular glial fibrillary acid protein but showed no obvious influence on expression level of Ki-67 protein (a cell proliferation marker). This study has provided in vitro evidence that nestin siRNA can effectively block nestin expression and reduce cell growth of the cultured C6 astrocytoma cells, strongly suggesting that nestin siRNA-induced suppression of tumor cell growth may provide a potential novel clinical therapy against CNS astroglioma events. (C) 2007 Elsevier B.V. All rights reserved.