蟛蜞菊内酯通过调节 TGF-β1/Smad 信号通路抑制乳腺癌的生长和转移

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmacy and Pharmacology Pub Date : 2024-08-02 DOI:10.1093/jpp/rgae065

Hui Li, Manting Hou, Ping Zhang, Lutong Ren, Yuanyuan Guo, Liang Zou, Junling Cao, Zhaofang Bai

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引用次数: 0

摘要

目的：乳腺癌是一种具有高侵袭性和高转移性的恶性肿瘤。TGF-β1诱导的上皮-间质转化（EMT）是乳腺癌生长和转移的关键因素。蟛蜞菊内酯（Wedelolactone，Wed）提取自中药Ecliptae Herba，据报道具有抗肿瘤活性。在此，我们旨在阐明 Wed 对乳腺癌的疗效和机制：方法：检测 Wed 对 4T1 迁移和侵袭的影响。方法：检测 Wed 对 4T1 迁移和侵袭的影响，并通过 Western 印迹和 qPCR 检测 EMT 相关标记物的表达。建立了4T1正位小鼠乳腺癌模型，以评估Wed通过TGF-β1/Smad通路对乳腺癌生长和转移的治疗效果：结果：Wed抑制了4T1的增殖、迁移和侵袭。结果：Wed 可抑制 4T1 的增殖、迁移和侵袭，对 p-Smad2/3 的抑制作用呈浓度依赖性。Wed 还能逆转 TGF-β1 诱导的 EMT 标志物的表达。此外，Wed 还能抑制小鼠乳腺癌的生长和转移。它还影响了p-Smad3以及EMT相关基因的表达，表明其抗乳腺癌作用可能与TGF-β1/Smad通路有关：结论：Wed通过调节TGF-β1/Smad通路逆转EMT，有可能成为乳腺癌的治疗药物。Wed有望成为抑制TGF-β1/Smad通路相关疾病的潜在药物。

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Wedelolactone suppresses breast cancer growth and metastasis via regulating TGF-β1/Smad signaling pathway.

Objective: Breast cancer is a malignant tumor with high invasion and metastasis. TGF-β1-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of breast cancer. Wedelolactone (Wed) is extracted from herbal medicine Ecliptae Herba, which is reported to have antineoplastic activity. Here, we aimed to elucidate the efficacy and mechanism of Wed against breast cancer.

Methods: The effects of Wed on migration and invasion of 4T1 were detected. The expression of EMT-related markers was detected by Western blot and qPCR. The 4T1 orthotopic murine breast cancer model was established to evaluate the therapeutic effect of Wed on the growth and metastasis of breast cancer through TGF-β1/Smad pathway.

Results: Wed inhibited the proliferation, migration and invasion of 4T1. It exhibited concentration-dependent inhibition of p-Smad2/3. Wed also reversed the expression of EMT-markers induced by TGF-β1. In addition, Wed suppressed the growth and metastasis of breast cancer in mice. It also affected p-Smad3 expression as well as EMT-related genes, suggesting that its anti-breast cancer effect may be related to the TGF-β1/Smad pathway.

Conclusion: Wed reverses EMT by regulating TGF-β1/Smad pathway, potentially serving as a therapeutic agent for breast cancer. Wed is expected to be a potential drug to inhibit TGF-β1/Smad pathway-related diseases.

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来源期刊

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.