Mechanism of Xiaojinwan Against Breast Cancer Bone Metastasis： An Exploration Based on Bioinformatic Analysis Combined with Cell Experiments
10.13422/j.cnki.syfjx.20211315
- VernacularTitle:生信分析联合实验验证探究小金丸治疗乳腺癌骨转移的机制
- Author:
Dan-dan FENG
1
;
Zhi-yong LIU
2
;
Guang-xi SHI
2
;
Yi-fei ZENG
3
;
Ying-jie QUAN
3
;
Xiao-fei LIU
1
;
Jing-wei LI
2
Author Information
1. The First Clinical Medical College of Shandong University of Traditional Chinese Medicine（TCM），Jinan 250014，China
2. Affiliated Hospital of Shandong University of TCM，Jinan 250014，China
3. College of TCM，Shandong University of TCM，Jinan 250014，China
- Publication Type:Research Article
- Keywords:
breast cancer;
bone metastasis;
Xiaojinwan;
network pharmacology;
molecular docking
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(21):188-197
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the mechanism of Xiaojinwan in treating breast cancer bone metastases through cell experiments and bioinformatic analysis. Method:The inhibitory effect of Xiaojinwan on MCF-7 cell viability was detected by cell counting kit-8 （CCK-8） assay. The key components and targets responsible for Xiaojinwan in inhibiting breast cancer bone metastases were predicted by network pharmacology and molecular docking. The active components and targets of Xiaojinwan were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCSMP） and SwissTarget Prediction， and the breast cancer bone metastases-related targets from GeneCards and DisGeNET. The results were imported into STRING for constructing a protein-protein interaction （PPI） network， followed by Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis using DAVID. A network of the active components of Xiaojinwan-breast cancer bone metastases-related targets-pathways was constructed using Cytoscape 3.7.2. AutoDock 4 was employed for molecular docking. The protein expression levels of matrix metallopmteinase-9 （MMP-9）， hypoxia-inducible factor 1α （HIF1A）， and androgen receptor （AR） were assayed by Western blot. Result:Xiaojinwan inhibited the viability of MCF-7 cells and acted on breast cancer bone metastases through such processes as redox and protein autophosphorylation. KEGG enrichment analysis showed that HIF-1， vascular endothelial growth factor （VEGF） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） pathways were involved. As verified by molecular docking， the active components such as eucalyptin stably bound to AR and MMP-9. Western blot indicated that Xiaojinwan dose-dependently inhibited the expression of MMP-9 and HIF1A proteins in MCF-7 cells. Conclusion:Xiaojinwan acts on AR and MMP-9 through HIF， VEGF and other related signaling pathways， thereby improving hypoxia in tumor microenvironment， inhibiting angiogenesis， and reducing cell invasion and viability.
