Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation.

Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation.
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DOI:
10.4062/biomolther.2016.044
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发表时间:
2017-03-01
影响因子:
3.7
通讯作者:
Zhong XY
Zhong XY
中科院分区:
医学3区
文献类型:
--
作者:
Ma JW;Zhang Y;Ye JC;Li R;Wen YL;Huang JX;Zhong XY

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粉防己碱(泰特)是一种双苄基异喹啉生物碱,对肿瘤有放射增敏作用。然而,其对人脑胶质瘤的作用及其具体的分子机制尚不清楚。在这项研究中,我们证明了泰特对人脑胶质瘤细胞具有放射增敏作用。有推测认为,泰特通过影响胶质瘤细胞周期和DNA修复机制对胶质瘤细胞具有放射增敏作用,并且ERK介导这些活性。因此,我们进行了详细的分析,泰特对细胞周期的影响,通过进行流式细胞仪分析和DNA修复,通过检测磷酸化H2 AX的表达,免疫荧光。我们用Western blot分析ERK在泰特影响细胞周期和DNA修复中的作用。结果表明,泰特通过抑制胶质瘤细胞增殖和降低磷酸化ERK及其下游蛋白的表达而发挥放射增敏作用。总之,我们的数据表明,ERK参与Tet-induced胶质瘤细胞的放射增敏通过抑制胶质瘤细胞增殖或细胞周期在G 0/G1期。
Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence. We used western blot analysis to investigate the role of ERK in the effect of Tet on the cell cycle and DNA repair. The results revealed that Tet exerts its radiosensitization effect on glioma cells by inhibiting proliferation and decreasing the expression of phosphorylated ERK and its downstream proteins. In summary, our data indicate that ERK is involved in Tet-induced radiosensitization of glioma cells via inhibition of glioma cell proliferation or of the cell cycle at G0/G1 phase.