Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka, Moscow Region, Russia.
Bull Exp Biol Med. 2024 Jul;177(3):318-322. doi: 10.1007/s10517-024-06181-1. Epub 2024 Aug 14.
We studied the expression of Nrf2 transcription factor and antioxidant system proteins in drug-resistant murine leukemia strains P388 in vivo, as well as the redox status of cells under conditions of induced oxidative stress. Immunoblotting and real-time PCR showed that the cyclophosphamide-resistant strain P388 (P388/CP) exhibits Nrf2-mediated drug resistance. Cells of the P388/CP strain are characterized by high expression of Nrf2, which leads to a significant increase in the expression of ARE genes and antioxidant system proteins, as well as to the effective maintenance of redox homeostasis under conditions of induced oxidative stress. Taking into account the important role of Nrf2 overexpression in reducing the effectiveness of chemotherapy in patients with different leukemias, the P388/CP strain can be of great interest as a model in the development of new drugs for the treatment of malignant neoplasms.
我们研究了 Nrf2 转录因子和抗氧化系统蛋白在体内耐药性小鼠白血病株 P388 中的表达，以及在诱导氧化应激条件下细胞的氧化还原状态。免疫印迹和实时 PCR 显示，环磷酰胺耐药株 P388（P388/CP）表现出 Nrf2 介导的耐药性。P388/CP 株细胞的特点是 Nrf2 表达水平高，导致 ARE 基因和抗氧化系统蛋白的表达显著增加，并在诱导氧化应激条件下有效维持氧化还原平衡。鉴于 Nrf2 过表达在降低不同白血病患者化疗效果方面的重要作用，P388/CP 株作为一种治疗恶性肿瘤的新药开发模型可能具有重要意义。
