Chaetocin通过靶向SH-SY5Y细胞中的JAK2/STAT3信号通路抑制神经母细胞瘤的进展。

IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Ke Wang, Ye Li, Linlin Wang
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引用次数: 0

摘要

柴胡素是一种真菌毒素,广泛存在于各种天然产品中,具有抗癌和抗炎活性。本文以SHSY-5Y人神经母细胞瘤细胞为研究对象,探讨了柴胡素对神经母细胞瘤进展的抗癌作用及其分子机制。研究了柴胡素对细胞活力、凋亡、细胞迁移和侵袭的影响。研究发现,柴胡素抗癌作用的基本机制是通过激活JAK2/STAT3信号通路介导的。此外,当SHSY-5Y细胞暴露于较高浓度的柴胡素时,通过增强促凋亡蛋白Bcl-2的表达,诱导细胞凋亡的作用显著增强,从而对神经母细胞瘤产生抗癌活性。此外,柴胡素在50 μM浓度下可明显降低SHSY-5Y细胞的侵袭和迁移。此外,研究还表明,增加柴胡素的剂量会大大降低与JAK2/STAT3信号通路相关的蛋白质的活性。总之,柴胡素对神经母细胞瘤细胞具有多种作用,包括抑制增殖、诱导凋亡、扰乱细胞形态和调节关键信号通路,尤其是对JAK/STAT3通路的作用。这些结果提供了宝贵的见解,强调了柴胡素在治疗神经母细胞瘤方面的潜在治疗作用,表明柴胡素对癌症进展所涉及的关键细胞过程具有多方面的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chaetocin inhibits the progression of neuroblastoma by targeting JAK2/STAT3 signaling pathway in SH-SY5Y cells.

Chaetocin is a fungal mycotoxin that extensively found in various natural products and has anticancer and anti‑inflammatory activities. Herein, the anticancer effects of chaetocin against the progression of neuroblastoma were studied with SHSY-5Y human neuroblastoma cells and examined the underlying molecular mechanisms. The effects of chaetocin on cellular viability, apoptosis, cell migration, and invasion were investigated. The underlying mechanism of anticancer effects of chaetocin was found to mediate via activating JAK2/STAT3 signaling pathway. Furthermore, when SHSY-5Y cells were exposed to a higher concentration of chaetocin, the induction of cell apoptosis significantly increased by enhancing the expression of pro-apoptotic protein Bcl-2, resulting in anticancer activity against neuroblastoma. In addition, chaetocin significantly decreased the SHSY-5Y cell invasion and migration at 50 μM treatment. Moreover, it was shown that increasing chaetocin treatments greatly decreased the activity of proteins connected to the JAK2/STAT3 signaling pathway. In conclusion, chaetocin exhibits a diverse range of actions on neuroblastoma cells, including the inhibition of proliferation, induction of apoptosis, perturbation of cellular morphology, and modulation of critical signaling pathways, with a specific focus on the JAK/STAT3 pathway. These results contribute valuable insights that underscore the potential therapeutic utility of chaetocin in the context of neuroblastoma treatment, suggesting its multifaceted impact on key cellular processes involved in cancer progression.

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来源期刊
CiteScore
6.20
自引率
5.60%
发文量
142
审稿时长
4-8 weeks
期刊介绍: Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.
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