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西黄丸通过抑制 TGF-β 信号通路抑制乳腺癌恶性进展并获得化疗增敏作用。

Xihuang pill suppresses breast cancer malignancy by inhibiting TGF-β signaling and acquires chemotherapy benefits.

机构信息

General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310014, Zhejiang Province, China; Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer, Hangzhou, 310000, Zhejiang Province, China.

Key Laboratory for Diagnosis and Treatment of Upper Limb Edema and Stasis of Breast Cancer, Hangzhou, 310000, Zhejiang Province, China; College of Pharmacy, Zhejiang University of Technology, Hangzhou, 310014, Zhejiang Province, China.

出版信息

J Ethnopharmacol. 2025 Jan 30;337(Pt 3):119000. doi: 10.1016/j.jep.2024.119000. Epub 2024 Oct 28.

DOI:10.1016/j.jep.2024.119000
PMID:39490714
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Breast cancer (BC) has an extremely high global incidence rate. The Xihuang pill (XHP), a traditional Chinese formula, originates from Hongxu Wang's "Life-Saving Manual of Diagnosis and Treatment of External Diseases" written during the Qing Dynasty. In this book, XHP, was first suggested as an anticancer treatment for BC. However, the regulatory mechanism of XHP on BC requires further investigated.

AIM OF THE STUDY

To assess the effects of XHP on BC and elucidate the underlying associated signaling network.

MATERIALS AND METHODS

The influence of XHP on cellular viability, proliferation, and apoptosis of MDA-MB-231 and BT-549 cells were examined. The ability to metastasize was evaluated using Transwell invasion and wound healing tests. Western blotting was used to examine the epithelial-mesenchymal transition (EMT) markers expression. RNA sequencing and bioinformatic analysis were utilized to investigate the regulation mechanism of XHP. A subcutaneous tumor model was developed to study the tumor-inhibitory effects of XHP or/and Doxorubicin (Dox) on BALB/c nude mice, and the EMT marker levels in tumor tissues were determined using immunohistochemical labeling.

RESULTS

XHP demonstrated anticancer effects on BC cells by suppressing cell proliferation, inducing cellular apoptosis, and inhibiting EMT progression. XHP may regulate the EMT via the TGF-β axis, as shown by RNA sequencing and Western blotting analysis. Furthermore, the combination of XHP and Dox had a stronger therapeutic effect on BC cell proliferation, apoptosis, and metastasis in both cellular and animal models.

CONCLUSIONS

We were the first to reveal that XHP abrogated EMT progression via modulating the TGF-β axis. Furthermore, the combination therapy of XHP and Dox presents a promising novel therapeutic candidate for BC patients.

摘要

民族药理学相关性

乳腺癌(BC)在全球的发病率极高。西黄丸(XHP)是一种传统的中药配方,源自清代王洪绪所著的《外科证治全生集》。在这本书中,XHP 首次被提议作为 BC 的抗癌治疗方法。然而,XHP 对 BC 的调节机制仍需要进一步研究。

研究目的

评估 XHP 对 BC 的影响,并阐明其潜在的相关信号网络。

材料与方法

检测 XHP 对 MDA-MB-231 和 BT-549 细胞的细胞活力、增殖和凋亡的影响。使用 Transwell 侵袭和划痕愈合试验评估转移能力。采用 Western blot 检测上皮间质转化(EMT)标志物的表达。利用 RNA 测序和生物信息学分析研究 XHP 的调节机制。建立皮下肿瘤模型,研究 XHP 或/和多柔比星(Dox)对 BALB/c 裸鼠肿瘤的抑制作用,并通过免疫组织化学标记检测肿瘤组织中 EMT 标志物的水平。

结果

XHP 通过抑制细胞增殖、诱导细胞凋亡和抑制 EMT 进展,对 BC 细胞表现出抗癌作用。RNA 测序和 Western blot 分析表明,XHP 可能通过 TGF-β 轴调节 EMT。此外,XHP 和 Dox 的联合治疗在细胞和动物模型中对 BC 细胞增殖、凋亡和转移具有更强的治疗效果。

结论

我们首次揭示 XHP 通过调节 TGF-β 轴来阻断 EMT 进展。此外,XHP 和 Dox 的联合治疗为 BC 患者提供了一种有前途的新型治疗候选药物。

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