Department of Neurosurgery, School of Medicine, Showa University, Hatanodai 1-5-8, Shinagawa-ku, Tokyo 142-8666, Japan.
Anticancer Res. 2012 Nov;32(11):4709-13.
Glioblastoma is a malignant brain tumor that is difficult to completely cure by surgical treatment alone. However, resistance to anticancer drugs and radiation may be acquired during treatment. For instance, miRNAs involved in regulating the expression of genes inducing apoptosis and other specific genes have been proposed for use, in order to induce the apoptosis of radioresistant cancer cells. A172 glioblastoma cells, expressing wild-type p53 were irradiated to a total dose of up to 60 Gy allowing us to analyze the activities of apoptosis-related proteins. The miR-34a expression levels in cells after irradiation at 30 and 60 Gy were 0.17- and 18.7-times the BCL2 and caspase-9 expression levels, respectively. The high miR-34a expression level in the cells after irradiation at 60 Gy reduced the p53 expression level. This study suggests that apoptosis might be promoted by regulating the action of miRNAs, even in cells that have acquired radioresistance.
胶质母细胞瘤是一种恶性脑肿瘤,单纯通过手术治疗很难完全治愈。然而,在治疗过程中可能会产生对抗癌药物和辐射的耐药性。例如,已经提出使用涉及调节诱导细胞凋亡和其他特定基因表达的 miRNA,以诱导放射抗性癌细胞的凋亡。用高达 60 Gy 的总剂量照射表达野生型 p53 的 A172 胶质母细胞瘤细胞,使我们能够分析与凋亡相关的蛋白质的活性。在 30 和 60 Gy 照射后细胞中的 miR-34a 表达水平分别是 BCL2 和 caspase-9 表达水平的 0.17-和 18.7 倍。在 60 Gy 照射后细胞中高 miR-34a 表达水平降低了 p53 表达水平。本研究表明,即使在获得放射抗性的细胞中,通过调节 miRNA 的作用也可能促进细胞凋亡。