| Jiang Xin,Liu Ye,Chang Pengyu,et al.Wortmannin enhances radiation sensitivity of malignant glioma cells[J].Chinese Journal of Radiological Medicine and Protection,2014,34(7):497-501 |
| Wortmannin enhances radiation sensitivity of malignant glioma cells |
| Received:August 14, 2013 |
| DOI：10.3760/cma.j.issn.0254-5098.2014.07.005 |
| KeyWords:Wortmannin PI3K signaling pathway Malignant glioma Radiation sensitivity Mitochondria apoptosis pathway |
| FundProject: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） |
| Author Name | Affiliation | E-mail | | Jiang Xin | Department of Radiotherapy, First Hospital of Jilin University, Changchun 130021, China | | | Liu Ye | 130021 长春, 吉林大学白求恩第一医院放疗科病理科 | | | Chang Pengyu | Department of Radiotherapy, First Hospital of Jilin University, Changchun 130021, China | | | Qu Yaqin | Department of Radiotherapy, First Hospital of Jilin University, Changchun 130021, China | | | Huang Wei | Department of Radiotherapy, First Hospital of Jilin University, Changchun 130021, China | | | Wang Lizhe | Department of Radiotherapy, First Hospital of Jilin University, Changchun 130021, China | | | Jiang Xinping | Department of Radiotherapy, First Hospital of Jilin University, Changchun 130021, China | | | Rui Ji | Department of Biochemistry and Molecular Biology, University of Louisville, USA | | | Xin Ying | 吉林大学病理生物学教育部重点实验室 | xinying13@126.com |
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| Abstract:: |
| 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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