Interferon-beta inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines.
Interferon-beta inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines.
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干扰素-β 可抑制五种神经胶质瘤细胞系的细胞周期 S 期的增殖和进展。
DOI：
10.1007/bf00177272
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发表时间：
1996
影响因子：
3.9
通讯作者：
Floyd-Smith,G
中科院分区：
文献类型：
--
作者：
Garrison,JI;Berens,ME;Shapiro,JR;Treasurywala,S;Floyd-Smith,G
在5种人脑胶质瘤细胞系（AO 2 V4、GJC、GJR、NN和NNR）和正常星形胶质细胞培养物（SC和TM）中评价IFN-β的生长抑制作用。所有5种胶质瘤细胞系均显示出对IFN-β的抗增殖反应，而正常胶质细胞无反应。10、100和500 U/ml的IFN-β作用12 d后，AO 2 V4细胞数分别相对减少30%、70%和80%。GJC和GJR细胞系也对所测试的最低浓度的IFN-β显著响应，并且在500 U/ml时，相对细胞数减少55%。NN和NNR细胞对IFN-β的反应性最低，在500 U IFN-β/ml时最大生长抑制率为30%。在用IFN-β处理后，A02 V4、GJC、GJR和正常星形胶质细胞均表达编码抗病毒蛋白、2-5A合成酶的mRNA，这表明IFN-β与所有四种细胞系上的受体结合并激活诱导抗病毒蛋白所需的信号转导途径。测定活细胞的相对数量表明，这些细胞均未表现出细胞活力的显著降低。由于对IFN-β的抗增殖应答主要不是由于细胞死亡，因此通过流式细胞术评价IFN-β对细胞周期进程的影响。所有处理的胶质瘤细胞系均显示S期细胞比例相对增加。AO 2 V4细胞的S期细胞百分比增加50%-80%，而GJC、GJR和NNR细胞的S期细胞百分比增加20%-40%。正常星形胶质细胞的IFN-β处理没有显著改变其细胞周期谱。这些数据表明，IFN-β通过阻止细胞周期的有序进程通过S期或减少进入G2/M期而发挥其对胶质瘤细胞的抗增殖作用。
The growth inhibitory effect of IFN-β was evaluated in 5 human glioma cell lines (AO2V4, GJC, GJR, NN and NNR) and in normal astrocyte cultures (SC and TM). All 5 glioma cell lines showed an anti-proliferative response to IFN-β whereas normal glial cells were non-responsive. IFN-β at 10, 100 and 500 U/ml lead to a 30%,70% and 80% relative decrease in cell number after 12 days, respectively in AO2V4 cells. GJC and GJR cell lines also responded significantly to the lowest concentration of IFN-β tested and at 500 U/ml the relative cell number decreased 55%. The NN and NNR cells were the least responsive to IFN-β with maximum growth inhibition of 30% at 500 U IFN-β/ml. Following treatment with IFN-β, AO2V4, GJC, GJR and normal astrocytes all expressed mRNA encoding the anti-viral protein, 2-5A synthetase demonstrating that IFN-β bound to receptors on all four cell lines and activated signal transduction pathways required for induction of an anti-viral protein. A determination of the relative number of viable cells showed that none of these cells exhibited a significant decrease in cell viability. Since the antiproliferative response to IFN-β was not primarily due to cell death, the effect of IFN-β on cell cycle progression was evaluated by flow cytometry. All treated glioma cell lines showed a relative increase in proportion of cells in S phase. AO2V4 cells had a 50%–80% increase in the percentage of cells in S phase, whereas GJC, GJR and NNR had percentage increases of 20%–40%. IFN-β treatment of normal astrocytes did not significantly alter their cell cycle profile. These data suggest that IFN-β exerts its antiproliferative effect on glioma cells by arresting the ordered progression through S phase or decreasing entry into G2/M phase of the cell cycle.