Liu Junfeng, Liu Yu, Xie Tao, Luo Longjun, Xu Cheng, Gao Qinglei, Shen Lu, Wan Feng, Lei Ting, Ye Fei
a Department of Neurosurgery , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , PR China.
b Cancer Biology Research Center (Key Laboratory of the Ministry of Education) , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , PR China.
Int J Radiat Biol. 2018 Apr;94(4):394-402. doi: 10.1080/09553002.2018.1440094. Epub 2018 Feb 27.
The purpose of this study is to systematically study the cell-cycle alterations of glioblastoma stem-like cells (GSLCs) after irradiation, possibly enriching the mechanisms of radioresistance of GSLCs.
GSLCs were enriched and identified, and then the radioresistance of GSLCs was validated by analyzing cell survival, cell proliferation, and radiation-induced apoptosis. The discrepancy of the cell-cycle distribution and expression of cell-cycle-related proteins between GSLCs and glioblastoma differentiated cells (GDCs) after irradiation was completely analyzed.
The survival fractions and the cell viabilities of GSLCs were significantly higher than those of GDCs after irradiation. Radiation-induced apoptosis was less prominent in GSLCs than in GDCs. After irradiation with high-dose X-rays, the percentages of GDCs in G2/M phase was evidently increased. However, radiation-induced G2/M arrest occurred less frequently in GSLCs, but S-phase arrest occurred in GSLCs after irradiation with 8 Gy. Further mechanistic studies showed that the expressions levels of Cdc25c, Cdc2, and CyclinB1 in GSLCs were not apparently changed after irradiation, while those of p-ATM and p-Chk1 were sharply increased after irradiation in GSLCs. The basal level of Cdc25c expression in GSLCs was much higher than that in GDCs.
We explored the cell-cycle alterations and cell-cycle-related proteins expression levels in GSLCs after irradiation, providing a novel mechanism of radioresistance of GSLCs.
本研究旨在系统地研究胶质母细胞瘤干细胞样细胞（GSLCs）在辐照后的细胞周期变化，可能丰富GSLCs的放射抗性机制。
富集并鉴定GSLCs，然后通过分析细胞存活、细胞增殖和辐射诱导的凋亡来验证GSLCs的放射抗性。全面分析辐照后GSLCs与胶质母细胞瘤分化细胞（GDCs）之间细胞周期分布和细胞周期相关蛋白表达的差异。
辐照后GSLCs的存活分数和细胞活力显著高于GDCs。辐射诱导的凋亡在GSLCs中不如在GDCs中明显。高剂量X射线辐照后，GDCs在G2/M期的百分比明显增加。然而，辐射诱导的G2/M期阻滞在GSLCs中发生的频率较低，但8 Gy辐照后GSLCs出现S期阻滞。进一步的机制研究表明，辐照后GSLCs中Cdc25c、Cdc2和CyclinB1的表达水平没有明显变化，而p-ATM和p-Chk1的表达水平在辐照后急剧增加。GSLCs中Cdc25c表达的基础水平远高于GDCs。
我们探索了辐照后GSLCs的细胞周期变化和细胞周期相关蛋白的表达水平，为GSLCs的放射抗性提供了一种新机制。
