Clynes M, Redmond A, Moran E, Gilvarry U
National Cell and Tissue Culture Centre/Bioresearch Ireland, Dublin City University, Glasnevin.
Cytotechnology. 1992;10(1):75-89. doi: 10.1007/BF00376102.
A 300-fold adriamycin resistant variant (DLKP-A) of the human lung squamous cell carcinoma line DLKP was established by stepwise selection in increasing concentrations of adriamycin. Different levels of cross-resistance were observed towards VP-16, VM-26, colchicine, vincristine and, somewhat unexpectedly, cis-platin. Resistance was stable for at least 3 months in culture in the absence of drug. P-glycoprotein overexpression was detected by immunofluorescence and Western Blotting, and a direct causal role for P-glycoprotein overexpression in the resistant phenotype was established by transfection with an mdr1 specific antisense oligonucleotide. A modified cryopreservation procedure was necessary for the resistant variant line. The resistant population displays clonal heterogeneity with respect to resistance level. A higher frequency of double minute chromosomes was observed in DLKP-A when compared with the parental cell line.
通过在浓度递增的阿霉素中逐步筛选，建立了人肺鳞癌细胞系DLKP的300倍阿霉素抗性变体（DLKP-A）。观察到对VP-16、VM-26、秋水仙碱、长春新碱以及有些出乎意料的顺铂存在不同程度的交叉抗性。在无药物培养的情况下，抗性至少稳定3个月。通过免疫荧光和蛋白质印迹检测到P-糖蛋白过表达，并且通过用mdr1特异性反义寡核苷酸转染确定了P-糖蛋白过表达在抗性表型中的直接因果作用。抗性变体系需要一种改良的冷冻保存程序。抗性群体在抗性水平方面表现出克隆异质性。与亲代细胞系相比，在DLKP-A中观察到双微小染色体的频率更高。
