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天然化合物 Byakangelicin 通过调节 SHP-1/JAK2/STAT3 信号通路抑制乳腺癌生长和迁移。

Natural compound Byakangelicin suppresses breast tumor growth and motility by regulating SHP-1/JAK2/STAT3 signal pathway.

机构信息

The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, China.

Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 201600, China.

出版信息

Biochem Biophys Res Commun. 2024 Apr 30;706:149758. doi: 10.1016/j.bbrc.2024.149758. Epub 2024 Mar 5.

DOI:10.1016/j.bbrc.2024.149758
PMID:38484571
Abstract

Byakangelicin mostly obtained from the root of Angelica dahurica and has protective effect on liver injury and fibrosis. In addition, Byakangelicin, as a traditional medicine, is also used to treat colds, headache and toothache. Recent studies have shown that Byakangelicin exhibits anti-tumor function; however, the role of Byakangelicin in breast tumor progression and related mechanism has not yet been elucidated. Our study aims to investigate the role of Byakangelicin in breast tumor progression and the underlying mechanism. To measure the effect of Byakangelicin on JAK2/STAT3 signaling, a dual luciferase reporter assay and a Western blot assay were performed. CCK8, colony formation, apoptosis and cell invasion assays were used to examine the inhibitory potential of Byakangelicin on breast cancer cells. Additionally, SHP-1 was silenced by specific siRNA duplex and the function of SHP-1 on Byakangelicin-mediated inhibition of JAK2/STAT3 signaling was evaluated. Byakangelicin treatment significantly inhibited STAT3 transcriptional activity. In addition, Byakangelicin treatment blocked JAK2/STAT3 signaling in a dose-dependent manner. Byakangelicin-treated tumor cells showed a dramatically reduced proliferation, colony formation and invasion ability. Moreover, Byakangelicin remarkedly induced breast cancer cell apoptosis. Furthermore, Byakangelicin regulated the expression of SHP1.In conclusion, our current study indicated that Byakangelicin, a natural compound, inhibits SHP-1/JAK2/STAT3 signaling and thus blocks tumor growth and motility.

摘要

白花前胡甲素主要从当归中提取,对肝损伤和纤维化有保护作用。此外,白花前胡甲素作为一种传统药物,也用于治疗感冒、头痛和牙痛。最近的研究表明,白花前胡甲素有抗肿瘤作用;然而,白花前胡甲素在乳腺肿瘤进展中的作用及其相关机制尚未阐明。我们的研究旨在探讨白花前胡甲素在乳腺肿瘤进展中的作用及其潜在机制。为了测量白花前胡甲素对 JAK2/STAT3 信号的影响,进行了双荧光素酶报告基因检测和 Western blot 检测。CCK8、集落形成、凋亡和细胞侵袭实验用于检测白花前胡甲素对乳腺癌细胞的抑制潜力。此外,通过特异性 siRNA 双链沉默 SHP-1,并评估 SHP-1 在白花前胡甲素介导的 JAK2/STAT3 信号抑制中的功能。白花前胡甲素处理显著抑制 STAT3 的转录活性。此外,白花前胡甲素处理以剂量依赖的方式阻断 JAK2/STAT3 信号。用白花前胡甲素处理的肿瘤细胞增殖、集落形成和侵袭能力明显降低。此外,白花前胡甲素显著诱导乳腺癌细胞凋亡。此外,白花前胡甲素调节 SHP1 的表达。总之,我们的研究表明,天然化合物白花前胡甲素抑制 SHP-1/JAK2/STAT3 信号,从而阻断肿瘤生长和迁移。

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