Time and dose-dependent radiosensitization of the glioblastoma multiforme U251 cells by the EGF receptor tyrosine kinase inhibitor ZD 1839 ('Iressa')
Time and dose-dependent radiosensitization of the glioblastoma multiforme U251 cells by the EGF receptor tyrosine kinase inhibitor ZD 1839 ('Iressa')
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DOI：
10.1016/j.canlet.2003.07.006
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发表时间：
2003-12-08
期刊：
影响因子：
9.7
通讯作者：
Martinez, JD
中科院分区：
文献类型：
--
作者：
Stea, B;Falsey, R;Martinez, JD
过度活跃的表皮生长因子受体（EGFR）信号通路促进不受调节的细胞生长并抑制细胞凋亡，被认为与多形性胶质母细胞瘤（GBM）的临床放射耐药有关。阻断EGFR信号通路可能提供一个有吸引力的治疗靶点，以增加放射治疗的细胞毒性作用。我们报道了选择性EGFR酪氨酸激酶抑制剂ZD1839 （Iressa）对表达高水平EGFR的U251 GBM细胞系辐射敏感性的影响。在辐射生存实验中，ZD1839的5mum具有显著的放射增敏作用，在ZD1839存在的5gy剂量下观察到细胞死亡增加。药物给药的剂量和时间表与放射结合似乎是获得细胞放射致敏的关键因素。这些研究为治疗GBM提供了新的治疗策略。2003爱思唯尔爱尔兰有限公司版权所有。
Hyperactive epidermal growth factor receptor (EGFR) signaling, which promotes unregulated cell growth and inhibits apoptosis, is believed to contribute to clinical radiation resistance of glioblastoma multiforme (GBM). Blockage of the EGFR signalling pathways may offer an attractive therapeutic target to increase the cytotoxic effects of radiotherapy. We report the effects of ZD1839 ('Iressa'), a selective EGFR tyrosine kinase inhibitor on the radiation sensitivity of the U251 GBM cell line, which expresses high levels of EGFR. In radiation survival experiments, 5 muM of ZD1839 had a significant radiosensitizing effect and increased cell death was observed at doses of 5 Gy in the presence of ZD1839. Dose and schedule of drug administration in combination with radiation appeared to be a crucial element to obtain radiosensitization of the cells. These studies suggest novel therapeutic strategies in the treatment of GBM. (C) 2003 Elsevier Ireland Ltd. All rights reserved.