DEVELOPMENT OF MULTIDRUG RESISTANCE IN A PRIMITIVE NEUROECTODERMAL TUMOR-CELL LINE
DEVELOPMENT OF MULTIDRUG RESISTANCE IN A PRIMITIVE NEUROECTODERMAL TUMOR-CELL LINE
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DOI：
10.3171/jns.1992.76.3.0502
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发表时间：
1992-03-01
影响因子：
4.1
通讯作者：
RAFFEL, C
中科院分区：
文献类型：
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作者：
TISHLER, DM;RAFFEL, C
耐药性仍然是小儿原始神经外胚层肿瘤成功治疗的一个巨大障碍。对化疗药物的耐药性可能部分与多药耐药基因1（MDR 1）的表达有关。该基因的蛋白质产物P-糖蛋白赋予对多种无关的抗肿瘤药物的抗性。来自原始神经外胚层肿瘤的细胞系DAOY被用作体外模型来检查耐药性的发展。通过DAOY在增加药物浓度中的生长来开发对放线菌素D具有抗性的细胞系。所得细胞系对放线菌素D的IC 50（诱导细胞生长减少50%所需的药物浓度）是亲本细胞系的10倍以上。耐药株系对VP-16（依托泊苷）交叉耐药，尽管之前没有暴露于该药物。在已知的P-糖蛋白抑制剂维拉帕米的存在下，放线菌素D的耐药性减弱。MDR 1基因在信使核糖核酸（RNA）和蛋白质水平上不被亲本DAOY系表达。通过RNA印迹和免疫印迹技术记录耐药株系中MDR 1基因的表达。这些结果表明，暴露于化疗药物可以诱导经典的多药耐药在原始神经外胚层肿瘤。
Drug resistance remains a formidable obstacle to the successful treatment of pediatric primitive neuroectodermal tumors. Resistance to chemotherapeutic agents may be related, in part, to expression of the multidrug resistance gene 1 (MDR1). The protein product of this gene, P-glycoprotein, confers resistance to multiple unrelated antineoplastic drugs.The cell line DAOY, derived from a primitive neuroectodermal tumor, was used as an in vitro model to examine the development of drug resistance. Cell lines resistant to actinomycin D were developed by the growth of DAOY in increasing concentrations of the drug. The IC50 (concentration of drug needed to induce a 50% reduction in cell growth) of the resultant lines to actinomycin D was more than 10 times that of the parental line. The resistant lines were cross-resistant to VP-16 (etoposide), despite lack of previous exposure to this drug. The resistance to actinomycin D was attenuated in the presence of verapamil, a known inhibitor of P-glycoprotein. The MDR1 gene was not expressed by the parental DAOY line at the messenger ribonucleic acid (RNA) and protein level. Expression of the MDR1 gene was documented in the resistant lines by RNA blot and immunoblot techniques. These results suggest that exposure to chemotherapeutic drugs can induce classical multidrug resistance in primitive neuroectodermal tumors.