Characterization of a new drug-resistant human myeloma cell line that expresses P-glycoprotein.
Characterization of a new drug-resistant human myeloma cell line that expresses P-glycoprotein.
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发表时间：
1986-10
期刊：
影响因子：
11.2
通讯作者：
William S. Dalton;B. G. Durie;David S. Alberts;J. H. Gerlach;A. Cress
中科院分区：
文献类型：
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作者：
William S. Dalton;B. G. Durie;David S. Alberts;J. H. Gerlach;A. Cress
多发性骨髓瘤是一种具有高初始化疗反应但由于出现耐药性而几乎无法治愈的疾病。通过将细胞连续暴露于逐渐增加剂量的多柔比星，从骨髓瘤细胞系RPMI 8226中选择多柔比星抗性人骨髓瘤细胞系（8226/Dox）。尽管在无药物培养基中生长，但抗性表型已保留超过2个月。耐药亚系对米托蒽醌、氨氯地平、足叶乙甙和长春新碱交叉耐药。8226/Dox细胞系对美法仑保持敏感，但获得了对地塞米松的间接敏感性。通过[14 C]多柔比星和高效液相色谱法测定，与敏感线相比，8226/Dox在1小时时细胞内多柔比星积累减少了54%。与敏感的亲本细胞系相比，耐药亚系中多柔比星的外排显著更大。使用免疫印迹技术的膜分析检测到耐药亚系中的整合膜蛋白P-糖蛋白（Mr 170，000）的表达增加。8226/Dox的细胞遗传学分析揭示了在亲本细胞系中未观察到的7 q异常。未观察到双分钟或均匀染色区域。耐药细胞系的药物敏感性/耐药模式与临床观察结果密切相关，表明该细胞系有可能作为多发性骨髓瘤耐药模型。
Multiple myeloma is a disease with a high initial chemotherapeutic response but virtually no cures due to emergence of drug resistance. A doxorubicin-resistant human myeloma cell line (8226/Dox) has been selected from the myeloma cell line RPMI8226 by continuously exposing cells to gradually increasing doses of doxorubicin. The resistant phenotype has been retained for over 2 months despite growth in drug-free medium. The resistant subline was cross-resistant to mitoxantrone, acronycine, etoposide, and vincristine. The 8226/Dox cell line remained sensitive to melphalan but acquired collateral sensitivity to dexamethasone. Intracellular doxorubicin accumulation, as measured by [14C]doxorubicin and high-performance liquid chromatography, was decreased by 54% at 1 h for 8226/Dox compared to the sensitive line. Efflux of doxorubicin was significantly greater in the resistant subline as compared to the sensitive parent cell line. Membrane analysis using immunoblotting techniques detected increased expression of the integral membrane protein P-glycoprotein (Mr 170,000) in the resistant subline. Cytogenetic analysis of 8226/Dox revealed a 7q-anomaly not seen in the parent cell line. No double minutes or homogeneously staining regions were observed. The drug sensitivity/resistance pattern of the resistant cell line correlates well with clinical observations indicating the potential of this cell line as a model for resistance in multiple myeloma.