Effect of STI-571 (imatinib mesylate) in combination with retinoic acid and γ-irradiation on viability of neuroblastoma cells
Effect of STI-571 (imatinib mesylate) in combination with retinoic acid and γ-irradiation on viability of neuroblastoma cells
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DOI：
10.1016/j.bbrc.2006.02.059
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发表时间：
2006-04-21
影响因子：
3.1
通讯作者：
Niemeyer, CM
中科院分区：
文献类型：
--
作者：
Rössler, J;Zambrzycka, I;Niemeyer, CM
神经母细胞瘤表达酪氨酸激酶受体c-Kit、PDGFR-α和-β-STI-571靶标。我们研究了STI-571与维甲酸(RA)和伽玛射线联合应用对体外培养的NB细胞活力的影响。应用RT-PCR法和FACS法检测6株NB细胞中酪氨酸激酶受体及其配体的表达。用四甲基偶氮唑盐比色法测定其对细胞活力的影响。20 mU M STI-571作用72 h后，所有6个NB细胞系的细胞活力均受到显著抑制，两个已经对10 mU M有反应的细胞系无论其mRNA状态或细胞表面C-Kit、PDGFR-α和-β的表达水平如何，均有反应。与9-顺式维甲酸共孵育细胞对STI-571的抑制作用。然而，9-顺式维甲酸的预处理导致NB细胞对STI-571和伽玛射线耐药。对于已完成伽玛射线治疗的巩固治疗患者，STI-571联合9-顺式维甲酸治疗NB可能是一种治疗策略。(C)2006 Elsevier Inc.保留所有权利。
Neuroblastoma (NB) expresses the tyrosine kinase receptors c-Kit, PDGFR-alpha and -beta-targets for STI-571. We investigated a possible combination therapy of STI-571 with retinoic acid (RA) and gamma-irradiation on NB cell viability in vitro. Expression of tyrosine kinase receptors and their ligands was examined in 6 NB cell lines by RT-PCR and FACS. The effect on cell viability was determined by MTT assay. Cell viability of all 6 NB cell lines was significantly inhibited after treatment with 20 mu M STI-571 for 72 h, two cell lines responding already to 10 mu M. Cell lines responded irrespective of their mRNA status or cell surface expression of C-Kit, PDGFR-alpha and -beta. Co-incubation with 9-cis RA sensitized cells to the inhibitory effects of STI-571. However, pre-treatment with 9-cis RA resulted in resistance of NB cell lines to STI-571 and gamma-irradiation. Treatment of NB with STI-571 in combination with 9-cis RA might be a therapeutic strategy for patients in consolidation therapy who have completed gamma-irradiation therapy. (c) 2006 Elsevier Inc. All rights reserved.