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| Mechanism research of astragaloside Ⅳ on drug-resistant strain of mouse lymphocytic leukemia based on p62-Nrf2 pathway |
| Hits 673 Download times 464 Received:July 24, 2021 |
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| DOI
10.11656/j.issn.1672-1519.2021.12.24 |
| Key Words
p62-Nrf2 signaling pathway;astragaloside Ⅳ;chemoresistance |
| Author Name | Affiliation | E-mail | | WANG Xiaoling | College of Integrated Traditional and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | YANG Xiaojuan | College of Integrated Traditional and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | ZHENG Qianqian | College of Integrated Traditional and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | HOU Mengxue | College of Integrated Traditional and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | WANG Xu | College of Integrated Traditional and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | WANG Tao | College of Integrated Traditional and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | wangtao6112@163.com |
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| Abstract
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| [Objective] To investigate the effect of astragaloside Ⅳ/AST Ⅳ on drug-resistant strain of mouse lymphocytic leukemia based on p62-Nrf2 pathway.[Methods] The drug-resistant leukemia model was replicated in vitro, and drug-resistant cells were divided into 6 groups, namely blank group, model group, AST Ⅳ group, VER group, ML385 group, and ML385+AST Ⅳ group. They were subsequently treated with drugs for 48 hours. CCK-8 assay and ROS quantification were performed to observe the effects of AST Ⅳ on drug-resistance. To analyze the reversal mechanism of AST Ⅳ on drug resistance, Flow cytometry was performed to detect the changes of cell cycle and apoptosis rate, and real time RT-PCR and Western blot were performed to detect the expression of p62, Nrf2, HO-1, bcl-2, bax and Caspase-3 in p62-Nrf2 pathway.[Results] AST Ⅳ could down regulate the expression of p62, HO-1, bcl-2/bax, but up regulate the expression of Caspase-3, resulting in that drug-resistant cells were more sensitive to cisplatin because of the decreased ROS level. The proliferation of drug-resistant cells was inhibited. The cell cycle showed S-phase, G2, M phase arrest and the apoptosis rate increased.[Conclusion] AST Ⅳ can have the effect of reversing drug-resistance of leukemia cells, which may be related to the regulation of p62-Nrf2 pathway. However, the co-regulation of multiple pathways in cell fate still needs to be discussed. |
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