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

Chaetocin inhibits the progression of neuroblastoma by targeting JAK2/STAT3 signaling pathway in SH-SY5Y cells.

作者信息

Wang Ke, Li Ye, Wang Linlin

机构信息

Department of Neurosurgery, 3201 Hospital, Hanzhong, 723000, China.

Department of Oncology, Kunming Children's Hospital, Kunming, 650000, China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):4237-4246. doi: 10.1007/s00210-024-03426-8. Epub 2024 Oct 24.

Abstract

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.

摘要

Chaetocin是一种真菌霉菌毒素,广泛存在于各种天然产物中,具有抗癌和抗炎活性。在此,我们用SHSY-5Y人神经母细胞瘤细胞研究了Chaetocin对神经母细胞瘤进展的抗癌作用,并探讨了其潜在的分子机制。研究了Chaetocin对细胞活力、凋亡、细胞迁移和侵袭的影响。发现Chaetocin的抗癌作用机制是通过激活JAK2/STAT3信号通路介导的。此外,当SHSY-5Y细胞暴露于较高浓度的Chaetocin时,通过增强促凋亡蛋白Bcl-2的表达,细胞凋亡诱导显著增加,从而产生针对神经母细胞瘤的抗癌活性。此外,在50μM处理时,Chaetocin显著降低了SHSY-5Y细胞的侵袭和迁移。此外,研究表明,增加Chaetocin处理可大大降低与JAK2/STAT3信号通路相关的蛋白质活性。总之,Chaetocin对神经母细胞瘤细胞表现出多种作用,包括抑制增殖、诱导凋亡、扰乱细胞形态以及调节关键信号通路,特别关注JAK/STAT3通路。这些结果提供了有价值的见解,强调了Chaetocin在神经母细胞瘤治疗中的潜在治疗效用,表明其对癌症进展中涉及的关键细胞过程具有多方面的影响。

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