Garrison J I, Berens M E, Shapiro J R, Treasurywala S, Floyd-Smith G
Department of Zoology, Arizona State University, Tempe 85208-1501, USA.
J Neurooncol. 1996 Dec;30(3):213-23. doi: 10.1007/BF00177272.
The growth inhibitory effect of IFN-beta 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-beta whereas normal glial cells were non-responsive. IFN-beta 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-beta tested and at 500 U/ml the relative cell number decreased 55%. The NN and NNR cells were the least responsive to IFN-beta with maximum growth inhibition of 30% at 500 U IFN-beta/ml. Following treatment with IFN-beta, AO2V4, GJC, GJR and normal astrocytes all expressed mRNA encoding the anti-viral protein, 2-5A synthetase demonstrating that IFN-beta 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-beta was not primarily due to cell death, the effect of IFN-beta 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-beta treatment of normal astrocytes did not significantly alter their cell cycle profile. These data suggest that IFN-beta 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.
在5种人胶质瘤细胞系（AO2V4、GJC、GJR、NN和NNR）以及正常星形胶质细胞培养物（SC和TM）中评估了β-干扰素的生长抑制作用。所有5种胶质瘤细胞系均显示出对β-干扰素的抗增殖反应，而正常神经胶质细胞无反应。在AO2V4细胞中，10、100和500 U/ml的β-干扰素在12天后分别导致细胞数量相对减少30%、70%和80%。GJC和GJR细胞系对所测试的最低浓度β-干扰素也有显著反应，在500 U/ml时，相对细胞数量减少55%。NN和NNR细胞对β-干扰素反应最小，在500 Uβ-干扰素/ml时最大生长抑制率为30%。用β-干扰素处理后，AO2V4、GJC、GJR和正常星形胶质细胞均表达了编码抗病毒蛋白2-5A合成酶的mRNA，这表明β-干扰素与所有这四种细胞系上的受体结合，并激活了诱导抗病毒蛋白所需的信号转导途径。对活细胞相对数量的测定表明，这些细胞均未表现出细胞活力的显著下降。由于对β-干扰素的抗增殖反应并非主要由于细胞死亡，因此通过流式细胞术评估了β-干扰素对细胞周期进程的影响。所有处理过的胶质瘤细胞系在S期的细胞比例相对增加。AO2V4细胞在S期的细胞百分比增加了50%-80%，而GJC、GJR和NNR的百分比增加了20%-40%。用β-干扰素处理正常星形胶质细胞并未显著改变其细胞周期分布。这些数据表明，β-干扰素通过阻止细胞周期中S期的有序进程或减少进入G2/M期来对胶质瘤细胞发挥抗增殖作用。
