| 姜新,刘野,常鹏宇,曲雅勤,黄巍,王立哲,蒋鑫萍,Rui Ji,辛颖.渥曼青霉素对胶质瘤细胞U251的辐射增敏作用[J].中华放射医学与防护杂志,2014,34(7):497-501 |
| 渥曼青霉素对胶质瘤细胞U251的辐射增敏作用 |
| Wortmannin enhances radiation sensitivity of malignant glioma cells |
| 投稿时间：2013-08-14 |
| DOI：10.3760/cma.j.issn.0254-5098.2014.07.005 |
| 中文关键词: 渥曼青霉素 PI3K信号通路 恶性胶质瘤 辐射敏感性 线粒体凋亡途径 |
| 英文关键词:Wortmannin PI3K signaling pathway Malignant glioma Radiation sensitivity Mitochondria apoptosis pathway |
| 基金项目:吉林省科技厅国际合作科研项目（20130413032GH；20140414035GH）；吉林省科技厅青年基金（20130522038JH）；吉林省发展和改革委员会基金（2010019-1） |
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| 摘要点击次数: 3081 |
| 全文下载次数: 2020 |
| 中文摘要: |
| 目的 利用渥曼青霉素（wortmannin，WM）抑制人恶性胶质瘤细胞U251磷脂酰肌醇-3-激酶（PI3K）通路的活性，探讨对U251细胞辐射敏感性的影响及可能的作用机制。方法 采用10 μmol/L WM预处理U251 2 h，并接受10 Gy X射线照射，检测PI3K/Akt信号通路的活性、集落形成率和凋亡的变化；通过Western blot方法检测凋亡相关蛋白活化型Caspase-3、Bax、Bcl-2及XIAP表达的变化。结果 10 μmol/L WM预处理2 h，明显抑制了U251细胞phospho-Akt的表达（t=0.000 1，P<0.01）。WM预处理联合X射线照射后，U251细胞的凋亡率由对照组和单纯照射组的（2.14±1.32）%和（11.5±2.9）%增加到（22.6±3.8）%，差异具有统计学意义（t=0.009 3、0.002 7，P<0.01）；集落形成率由对照组和单纯照射组的（88.54±4.76）%和（56.31±4.05）%降低到（12.25±9.59）%（t=0.000 03、0.000 2，P<0.01）；同时伴随着凋亡相关蛋白活化型Caspase-3表达显著增加，Bax/Bcl-2的比值明显增高以及XIAP的显著降低。结论 WM通过抑制PI3K/Akt信号通路活性，增加凋亡蛋白Caspase-3的活化和Bax/Bcl-2比值，下调凋亡抑制蛋白XIAP来增强恶性胶质瘤细胞的辐射敏感性。 |
| 英文摘要: |
| Objective To explore the effect of wortmannin (WM), an inhibitor of PI3K signaling pathway, on the radiation sensitivity of human malignant glioma cells (U251) and the underlying mechanism.Methods U251 cells were pretreated with 10 μmol/L WM for 2 h and irradiated with 10 Gy X-rays, then the activity of PI3K/Akt signaling pathway, the colony-forming ability and apoptosis were detected to evaluate the effect of WM on radiosensitivity. The protein expressions of cleaved Caspase-3, Bax, Bcl-2 and XIAP were detected with Western blot assay. Results The expression of phospho-Akt was significantly inhibited by the pretreatment of cells with 10 μmol/L WM (t=0.000 1, P<0.01). The ratio of apoptotic cells in the WM+IR group was significantly increased from (2.14±1.32)% of control group and (11.5±2.9)% of IR group to (22.6±3.8)% (t=0.009 3, 0.002 7, P<0.01). The colony-forming rate of WM+IR group was decreased from (88.54±4.76)% of control group and (56.31±4.05)% of IR group to (12.25±9.59)% significantly (t=0.000 03, 0.000 2, P<0.01) accompanied with the increases of Caspase-3 and Bax/Bcl-2 but decrease of XIAP. Conclusions WM significantly increased the radiation sensitivity of human malignant glioma cells by inhibiting the activity of PI3K signaling pathway and the expressions of Bcl-2 and XIAP and activating Caspase-3 and Bax. |
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