{"title":"体内耐药 P388 株鼠白血病细胞中的 Nrf2 调节的抗氧化系统","authors":"A A Balakina, T A Raevskaya, V I Amozova","doi":"10.1007/s10517-024-06181-1","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":9331,"journal":{"name":"Bulletin of Experimental Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":0.9000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Nrf2-Regulated Antioxidant System in Cells of In Vivo Drug-Resistant P388 Murine Leukemia Strains.\",\"authors\":\"A A Balakina, T A Raevskaya, V I Amozova\",\"doi\":\"10.1007/s10517-024-06181-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":9331,\"journal\":{\"name\":\"Bulletin of Experimental Biology and Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.9000,\"publicationDate\":\"2024-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bulletin of Experimental Biology and Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10517-024-06181-1\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bulletin of Experimental Biology and Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10517-024-06181-1","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/14 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
我们研究了耐药小鼠白血病菌株P388体内Nrf2转录因子和抗氧化系统蛋白的表达,以及细胞在诱导氧化应激条件下的氧化还原状态。免疫印迹和实时聚合酶链式反应显示,环磷酰胺耐药株P388(P388/CP)表现出Nrf2介导的耐药性。P388/CP 株的细胞具有高表达 Nrf2 的特点,这导致 ARE 基因和抗氧化系统蛋白的表达显著增加,并在诱导氧化应激的条件下有效维持氧化还原平衡。考虑到 Nrf2 过度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 菌株作为治疗恶性肿瘤新药的开发模型具有重要意义。
Nrf2-Regulated Antioxidant System in Cells of In Vivo Drug-Resistant P388 Murine Leukemia Strains.
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.
期刊介绍:
Bulletin of Experimental Biology and Medicine presents original peer reviewed research papers and brief reports on priority new research results in physiology, biochemistry, biophysics, pharmacology, immunology, microbiology, genetics, oncology, etc. Novel trends in science are covered in new sections of the journal - Biogerontology and Human Ecology - that first appeared in 2005.
World scientific interest in stem cells prompted inclusion into Bulletin of Experimental Biology and Medicine a quarterly scientific journal Cell Technologies in Biology and Medicine (a new Russian Academy of Medical Sciences publication since 2005). It publishes only original papers from the leading research institutions on molecular biology of stem and progenitor cells, stem cell as the basis of gene therapy, molecular language of cell-to-cell communication, cytokines, chemokines, growth and other factors, pilot projects on clinical use of stem and progenitor cells.
The Russian Volume Year is published in English from April.