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补肾活血汤治疗乳腺癌分子机制的研究:网络药理学与实验

Insights into the Molecular Mechanisms of Bushen Huoxue Decoction in Breast Cancer Network Pharmacology and experiments.

作者信息

Liang Hongyi, Yin Guoliang, Shi Guangxi, Liu Xiaofei, Liu Zhiyong, Li Jingwei

机构信息

Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

出版信息

Curr Comput Aided Drug Des. 2025;21(1):50-66. doi: 10.2174/0115734099269728231115060827.

Abstract

AIMS

Breast cancer (BC) is by far seen as the most common malignancy globally, with 2.261 million patients newly diagnosed, accounting for 11.7% of all cancer patients, according to the Global Cancer Statistics Report (2020). The luminal A subtype accounts for at least half of all BC diagnoses. According to TCM theory, Bushen Huoxue Decoction (BSHXD) is a prescription used for cancer treatment that may influence luminal A subtype breast cancer (LASBC).

OBJECTIVES

To analyze the clinical efficacy and underlying mechanisms of BSHXD in LASBC.

MATERIALS AND METHODS

Network pharmacology and experiments were utilized to foresee the underlying mechanism of BSHXD for LASBC.

RESULTS

According to the bioinformatics analysis, BSHXD induced several proliferation and apoptosis processes against LASBC, and the presumed targets of active components in BSHXD were mainly enriched in the HIF-1 and PI3K/AKT pathways. Flow cytometry assay and western blotting results revealed that the rate of apoptosis enhanced in a dose-dependent manner with BSHXD concentration increasing, respectively. BSHXD notably downregulated the expressions of HIF-1α, P-PI3K, PI3K, P-AKT and AKT proteins. However, adding an HIF-1α agonist restored those protein levels.

CONCLUSION

The study proved that the mechanism of BSHXD in LASBC may be connected to suppressing proliferation by inhibiting the activity of the HIF-1α/PI3K/AKT signaling pathway and promoting apoptosis via the Caspase cascade in LASBC cells.

摘要

目的

乳腺癌是目前全球最常见的恶性肿瘤,根据《2020年全球癌症统计报告》,全球有226.1万例新诊断患者,占所有癌症患者的11.7%。腔面A型亚型至少占所有乳腺癌诊断病例的一半。根据中医理论,补肾活血汤(BSHXD)是一种用于癌症治疗的方剂,可能对腔面A型乳腺癌(LASBC)产生影响。

目的

分析补肾活血汤治疗LASBC的临床疗效及潜在机制。

材料与方法

采用网络药理学和实验方法预测补肾活血汤治疗LASBC的潜在机制。

结果

生物信息学分析显示,补肾活血汤对LASBC具有多种增殖和凋亡作用,其活性成分的假定靶点主要富集于HIF-1和PI3K/AKT信号通路。流式细胞术检测和蛋白质印迹结果显示,随着补肾活血汤浓度的增加,细胞凋亡率呈剂量依赖性升高。补肾活血汤显著下调HIF-1α、P-PI3K、PI3K、P-AKT和AKT蛋白的表达。然而,添加HIF-1α激动剂可恢复这些蛋白水平。

结论

本研究证明,补肾活血汤治疗LASBC的机制可能与通过抑制HIF-1α/PI3K/AKT信号通路的活性抑制增殖以及通过半胱天冬酶级联反应促进LASBC细胞凋亡有关。

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