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Pharmacological Mechanism of Mume Fructus in the Treatment of Triple-Negative Breast Cancer Based on Network Pharmacology

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Abstract

Our study aims to find the relevant mechanism of Mume Fructus in the treatment of triple-negative breast cancer (TNBC) by network pharmacology analysis and experimental validation. The effective compounds of Mume Fructus and TNBC-related target genes were imported into Cytoscape to construct a Mume Fructus-effective compounds-disease target network. The common targets of Mume Fructus and TNBC were determined by drawing Venn diagrams. Then, the intersection targets were transferred to the STRING database to construct a protein–protein interaction (PPI) network. To investigate the mechanism of Mume Fructus in treatment of TNBC, breast cancer cell (MDA-MB-231) was treated with Mume Fructus and/or transfected with small interference RNA-PKM2(siPKM2). CCK-8 assay, cell clonal formation assay, transwell, flow cytometry, qRT-PCR, and western blotting were performed. Eight effective compounds and 145 target genes were obtained, and the Mume Fructus- effective compounds-disease target network was constructed. Then through the analysis of the PPI network, we obtained 10 hub genes including JUN, MAPK1, RELA, AKT1, FOS, ESR1, IL6, MAPK8, RXRA, and MYC. KEGG enrichment analysis showed that JUN, MAPK1, RELA, FOS, ESR1, IL6, MAPK8, and RXRA were enriched in the Th17 cell differentiation signaling pathway. Loss of PKM2 and Mume Fructus both inhibited the malignant phenotype of MDA-MB-231 cells. And siPKM2 further aggravated the Mume Fructus inhibition of malignancy of breast cancer cells. Network pharmacology analysis suggests that Mume Fructus has multiple therapeutic targets for TNBC and may play a therapeutic role by modulating the immune microenvironment of breast cancer.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Change history

Abbreviations

TNBC:

Triple-negative breast cancer

Id-1:

DNA and mRNA binding factor

TILs:

Tumor-infiltrating lymphocytes

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Acknowledgements

We are thankful to Dr. Yuting Jiang for critically editing the current manuscript.

Funding

This work was supported by the Shandong Province Traditional Chinese Medicine Science and Technology Project, (2020M065); the Shandong Province School Health Association Project, (SDWS2022068) and the Shandong Province Traditional Chinese Medicine Science and Technology Project, (2017-263).

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  1. Lei Yin and Yan Qi contributed equally to the study.

Authors and Affiliations

  1. Department of Breast Surgery, The Second Affiliated Hospital of Shandong First Medical University, Taian, China

    Lei Yin

  2. Operating Theater of the Second Affiliated Hospital of Shandong First Medical University, Taian, China

    Yan Qi

  3. Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, China

    Yuting Jiang

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  1. Lei Yin
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  2. Yan Qi
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Yin, L., Qi, Y. & Jiang, Y. Pharmacological Mechanism of Mume Fructus in the Treatment of Triple-Negative Breast Cancer Based on Network Pharmacology. Appl Biochem Biotechnol (2024). https://doi.org/10.1007/s12010-024-04948-w

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