Le Moyec L, Tatoud R, Degeorges A, Calabresse C, Bauza G, Eugène M, Calvo F
Laboratoire de RMN et Exploration Fonctionnelle, Hopital Saint Louis, Paris, France.
Cancer Res. 1996 Aug 1;56(15):3461-7.
Proton nuclear magnetic resonance spectroscopy was performed on whole cells to study lipids and metabolites in Adriamycin- and Taxol-resistant K562 cells expressing multidrug resistance (MDR) and their sensitive counterparts. With one-dimensional spectra, both resistant cell lines showed lower fatty acid methylene:methyl ratios and higher choline:methyl ratios than sensitive cells. Using two-dimensional COSY spectra, a decrease in the glutamine content was evidenced in resistant cells. When these cells were maintained in culture medium without the drug, the fatty acid signals were partially recovered. Adriamycin-resistant K562 cells were also treated for 4 days with a high dose of verapamil, a MDR-reversing agent. The nuclear magnetic resonance spectra of verapamil-treated cells also showed partial recovery of fatty acid signals. These results could be paralleled with the reversion of the resistant phenotype, as evidenced by measuring the inhibiting concentration of Adriamycin and vinblastine in K562adr cells cultured without the drug or after short-term exposure to verapamil. Conversely, P-glycoprotein and mRNA expression and DNA amplification of the mdr gene were not modified when compared to resistant cells, suggesting that the MDR phenotype could be partially reversed independently of the mdr gene amplification and expression. These results demonstrate the role of lipids in the resistance phenomenon.
采用质子核磁共振波谱法对全细胞进行检测，以研究表达多药耐药性（MDR）的阿霉素和紫杉醇耐药K562细胞及其敏感对照细胞中的脂质和代谢产物。在一维谱图中，与敏感细胞相比，两种耐药细胞系均表现出较低的脂肪酸亚甲基:甲基比率和较高的胆碱:甲基比率。利用二维COSY谱图，证实耐药细胞中谷氨酰胺含量降低。当这些细胞在无药物的培养基中培养时，脂肪酸信号部分恢复。对阿霉素耐药的K562细胞还用高剂量的维拉帕米（一种MDR逆转剂）处理4天。维拉帕米处理细胞的核磁共振谱图也显示脂肪酸信号部分恢复。通过测量在无药物培养或短期暴露于维拉帕米后的K562adr细胞中阿霉素和长春碱的抑制浓度，这些结果与耐药表型的逆转情况相似。相反，与耐药细胞相比，P-糖蛋白、mdr基因的mRNA表达和DNA扩增未发生改变，这表明MDR表型可部分独立于mdr基因扩增和表达而逆转。这些结果证明了脂质在耐药现象中的作用。
