布福他林通过阻断胶质母细胞瘤的 ITGB4/FAK/ERK 通路诱导氧化应激介导的细胞凋亡

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Junchao Tan, Guoqiang Lin, Rui Zhang, Yuting Wen, Chunying Luo, Ran Wang, Feiyun Wang, Shoujiao Peng, Jiange Zhang
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引用次数: 0

摘要

布福他林(BT)是蟾酥的一种主要活性成分,具有多种药理活性。虽然以前的研究表明 BT 可以抑制胶质母细胞瘤(GBM)的生长,但 BT 在体内的安全性和潜在机制仍不清楚。我们进行了一项系统评估,研究 BT 对 GBM 细胞活力、迁移、侵袭和集落形成的影响。此外,我们还获得了体内结果,以评估 BT 对肿瘤生长的影响。我们的初步研究结果表明,BT 能有效抑制小鼠 GBM 细胞的生长和皮下肿瘤的形成,并能观察到可耐受的程度。从机理上讲,BT 治疗可诱导线粒体功能障碍、活性氧(ROS)爆发以及随后的细胞凋亡。更重要的是,基于蛋白质组学的差异表达蛋白分析表明,BT 治疗后整合素 β4(ITGB4)显著下调。此外,我们的证据表明,ITGB4/病灶粘附激酶(FAK)/细胞外信号相关激酶(ERK)通路参与了 BT 诱导的细胞凋亡。总之,我们的研究证明了 BT 的抗 GBM 作用,并阐明了其潜在机制,突出表明 BT 是治疗 GBM 的一种潜在选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bufotalin Induces Oxidative Stress-Mediated Apoptosis by Blocking the ITGB4/FAK/ERK Pathway in Glioblastoma.

Bufotalin (BT), a major active constituent of Chansu, has been found to possess multiple pharmacological activities. Although previous studies have shown that BT could inhibit the growth of glioblastoma (GBM), the safety of BT in vivo and the potential mechanism are still unclear. We conducted a systematic assessment to investigate the impact of BT on GBM cell viability, migration, invasion, and colony formation. Furthermore, in vivo results were obtained to evaluate the effect of BT on tumor growth. The preliminary findings of our study demonstrate the effective inhibition of GBM cell growth and subcutaneous tumor development in mice by BT, with tolerable levels of tolerance observed. Mechanistically, BT treatment induced mitochondrial dysfunction, bursts of reactive oxygen species (ROS), and subsequent cell apoptosis. More importantly, proteomic-based differentially expressed proteins analysis revealed a significant downregulation of integrin β4 (ITGB4) following BT treatment. Furthermore, our evidence suggested that the ITGB4/focal adhesion kinase (FAK)/extracellular signal-related kinase (ERK) pathway involved BT-induced apoptosis. Overall, our study demonstrates the anti-GBM effects of BT and elucidates the underlying mechanism, highlighting BT as a potential therapeutic option for GBM.

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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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