Balakina A A, Raevskaya T A, Pavlov V S, Mumyatova V A, Goncharova S A, Terent'ev A A
Institute of Problems Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow Region, Russia.
Scientific And Educational Center "Medical Chemistry", Moscow Regional State University, Mytishchi, Moscow Region, Russia.
Bull Exp Biol Med. 2019 Jul;167(3):339-342. doi: 10.1007/s10517-019-04522-z. Epub 2019 Jul 26.
Activities of superoxide dismutase and catalase and content of reduced glutathione in cells of drug-resistant murine leukemia P388 strains were studied without or after administration of antitumor compounds. In the absence of chemotherapeutic agents, no significant differences in activities of the studied enzymes in cells of the initial strain and strains resistant to cyclophosphamide, cisplatin, and rubomycin were observed. Compounds to which resistance was developed did not significantly affect activity of enzymes in cells of drug-resistant strains, while the use of compounds that were not resistance inductors was accompanied by a significant decrease in enzyme activity in cells resistant to cisplatin and rubomycin. In cells of strains resistant to cisplatin and cyclophosphamide, the content of reduced glutathione significantly differed from that in the initial strain. In addition, the concentration of reduced glutathione in cells of cyclophosphamide-resistant strain considerably decreased upon addition of the drug producing a therapeutic effect. Our findings suggest that the mechanism of resistance of in vivo derived cyclophosphamide resistant cell strain is related to increased level of reduced glutathione and activity of its metabolism.
在给予或未给予抗肿瘤化合物的情况下，研究了耐药性小鼠白血病P388菌株细胞中超氧化物歧化酶和过氧化氢酶的活性以及还原型谷胱甘肽的含量。在没有化疗药物的情况下，未观察到初始菌株以及对环磷酰胺、顺铂和柔红霉素耐药的菌株细胞中所研究酶的活性有显著差异。产生耐药性的化合物对耐药菌株细胞中的酶活性没有显著影响，而使用非耐药诱导剂化合物会导致对顺铂和柔红霉素耐药的细胞中酶活性显著降低。在对顺铂和环磷酰胺耐药的菌株细胞中，还原型谷胱甘肽的含量与初始菌株有显著差异。此外，在加入产生治疗效果的药物后，对环磷酰胺耐药菌株细胞中的还原型谷胱甘肽浓度大幅降低。我们的研究结果表明，体内衍生的环磷酰胺耐药细胞株的耐药机制与还原型谷胱甘肽水平及其代谢活性的增加有关。
