[1]张春满 郑云峰 米娟.BRAF 抑制剂PLX4032和放疗联合治疗高级神经胶质瘤[J].卒中与神经疾病杂志,2016,23(02):98-101.[doi:10.3969/j.issn.1007-0478.2016.02.007]
　Zhang Chunman,Zheng Yunfeng,Mi Juan..The effect of combining BRAF inhibitor PLX4032 and radiation in advanced glioma[J].Stroke and Nervous Diseases,2016,23(02):98-101.[doi:10.3969/j.issn.1007-0478.2016.02.007]
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BRAF 抑制剂PLX4032和放疗联合治疗高级神经胶质瘤(/HTML)
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第23卷
期数:
2016年02期
页码:
98-101
栏目:
论 著
出版日期:
2016-04-26

文章信息/Info

Title:
The effect of combining BRAF inhibitor PLX4032 and radiation in advanced glioma
作者:
张春满 郑云峰 米娟
作者单位:716000 延安大学附属医院神经外科[张春满(通信作者)郑云峰 米娟]
Author(s):
Zhang Chunman;  Zheng Yunfeng;  Mi Juan.
Department of Neurosurgery, Affiliated Hospital of Yanan University, Yanan 716000
关键词:
BRAF抑制剂 放疗 神经胶质瘤
Keywords:
BRAF inhibitor Radiation therapy Glioma
分类号:
R739.4
DOI:
10.3969/j.issn.1007-0478.2016.02.007
文献标志码:
A
摘要:
目的 探讨BRAF抑制剂PLX4032联合放疗对高级别神经胶质瘤的疗效。方法 选择两株细胞分别为AM-38(BRAF V600E)和GBM8(BRAF wildtype),用Cell Titre Glo 方法检测细胞的IC50; 用克隆形成实验检测PLX4032对不同放射剂量的增敏作用; 用流式细胞仪检测PLX4032和放疗对细胞凋亡和周期的作用。结果 PLX4032显著抑制BRAF V600E 细胞的增殖(IC50=2 μM)而对野生型细胞没有作用; 克隆形成实验发现在BRAF V600E 细胞上随着剂量增加,联合治疗组比单独放疗组的抑制作用更显著(P<0.05),而野生型细胞株上联合组和单独放疗组没有显著性差异(P>0.05); 流式细胞分析发现在BRAF V600E突变细胞上,联合治疗组细胞凋亡数显著增加,与对照组和单独治疗组相比有显著差异(P<0.05),而在野生型细胞株上没有显著性差异; 流式分析发现在BRAF V600E突变细胞上,与对照组相比,单独放疗组和联合治疗组在G0/G1期细胞数都减少,G2/M 期细胞数增加,而且联合治疗组与单独放疗组相比有显著差异。结论 BRAF抑制剂PLX4032 与放疗联合治疗BRAF V600E突变的高级别神经胶质瘤的疗效较好。
Abstract:
ObjectiveTo investigate the role of BRAF inhibitor PLX4032 in combination with radiotherapy on advanced glioma.Methods BRAF V600E-mutated cancer cell line(AM-38)and BRAFV600E wild-type cancer cell line(GBM8)were obtained. We performed cell viability assay to detect the IC50 of the inhibitor PLX4032 by the Cell Titre Glo assay and clonogenic assays using combinations of radiation and PLX4032. Cell apoptosis and cell cycle were evaluated by flow cytometry.Results PLX4032 significantly inhibited the proliferation of BRAF V600E cells(IC50 = 2 μM)and had no effect on wild-type cells. By clonogenic assay, combination group had more significant inhibitory effect than radiotherapy alone group for BRAF V600E cells with increasing dose(P<0.05), while there was no significant difference(P>0.05)on the wild-type cell lines between radiotherapy alone group and the combination group. For apoptosis, flow cytometry analysis showed that cell apoptosis proportion of combination group were significantly different compared to the control group and alone group in the BRAF V600E cells(P<0.05), whereas there’s no significant differences in the wild-type cell lines. For the cell cylcle, flow analysis found that alone and combined groups have reduced the number of G0/G1 phase of the cell and caused the cell G2/M phase arrest compared to the control group in the BRAF V600E mutated cell. There were significant difference between the combination group and alone groups.Conclusion These studies provide the pre-clinical rationale for clinical trials of concurrent radiotherapy and BRAF V600E inhibitors.

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备注/Memo

备注/Memo:
(2015-12-09收稿)
更新日期/Last Update: 2016-05-04