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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2023, Vol. 28 ›› Issue (12): 1321-1330.doi: 10.12092/j.issn.1009-2501.2023.12.001

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Mechanism of Pingxiao capsule promoting breast cancer apoptosis through AKT1/β-catenin signal based on network pharmacology

CHEN Hongxiao 1,2, LIU Su 2, JIN Le 2, ZHANG Huihui 3, ZHANG Lei 2, CHEN Zhaolin 1,2   

  1. 1 School of Pharmacy Anhui Medical University, Hefei 230032, Anhui,  China; 2 The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui, China; 3 Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Hefei 230032, Anhui, China
  • Received:2023-06-21 Revised:2023-08-07 Online:2023-12-26 Published:2023-12-21

Abstract:

AIM: To explore the potential mechanism of action of Pingxiao capsule in the treatment of breast cancer. METHODS: TCMSP, TCM-ID, GeneCards and other databases were used to screen the related targets of Pingxiao capsule and breast cancer. Cytoscape software builds drug-target-disease networks. R software was used for GO and KEGG analysis. Autodock Vina and Pymol software were used for molecular docking and visualization of Pingxiao capsule active ingredients and core targets. Core targets were analyzed by R software survival package, and genes closely related to overall survival time were screened out. Cell viability was detected by CCK-8 method. Flow cytometry was used to detect cell apoptosis. The protein expression levels of p-AKT1, β-catenin and cyclinD1 were detected by Western blot. RESULTS: A total of 194 drug targets were screened, 1612 disease targets were identified, 127 intersection targets were identified by Venn diagram, and 20 core targets were TB53, AKT1, TNF, CASP3, etc. GO analysis was mainly related to oxidative stress response, cell regulation of chemical reaction and other biological activities. KEGG analysis was mainly related to PI3K-AKT signaling pathway, TNF signaling pathway, IL-17 signaling pathway and other pathways. Molecular docking results showed that the active constituents were well combined with the core targets AKT1, MAPK1 and RELA. Cell experiments showed that quercetin (40, 80, 120 μmol/L) promoted apoptosis of breast cancer cells. Western blot analysis showed that the protein expressions of p-AKT1, β-catenin and cyclinD1 decreased with different concentrations of quercetin treated for 48h. CONCLUSION: Network pharmacology and cell experiments confirmed that Pingxiao capsule may exert its anti-breast cancer effect by regulating AKT1/β-catenin signaling pathway. 

Key words: Pingxiao capsule, breast cancer, network pharmacology, molecular docking, AKT1/β-catenin

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