Active substance and mechanisms of Actinidia chinensis Planch for the treatment of breast cancer was explored based on network pharmacology and in silico study.

In this paper, our objective was to investigate the potential mechanisms of Actinidia chinensis Planch (ACP) for breast cancer treatment with the application of network pharmacology, molecular docking, and molecular dynamics. "Mihoutaogen" was used as a key word to query the Traditional Chinese Medicine Systems Pharmacology database for putative ingredients of ACP and its related targets. DrugBank, GeneCards, Online Mendelian Inheritance in Man, and therapeutic target databases were used to search for genes associated with "breast cancer." Using Cytoscape 3.9.0 we then constructed the protein-protein interaction and drug-ingredient-target-disease networks. An enrichment analysis of Kyoto encyclopedia of genes and genomes pathway and gene ontology were performed to exploration of the signaling pathways associated with ACP for breast cancer treatment. Discovery Studio software was applied to molecular docking. Finally, the ligand-receptor complex was subjected to a 50-ns molecular dynamics simulation using the Desmond_2020.4 tools. Six main active ingredients and 176 targets of ACP and 2243 targets of breast cancer were screened. There were 118 intersections of targets for both active ingredients and diseases. Tumor protein P53 (TP53), AKT serine/threonine kinase 1 (AKT1), estrogen receptor 1 (ESR1), Erb-B2 receptor tyrosine kinase 2 (ERBB2), epidermal growth factor receptor (EGFR), Jun Proto-Oncogene (JUN), and Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) selected as the most important genes were used for verification by molecular docking and molecular dynamics simulation. The primary active compounds of ACP against breast cancer were predicted preliminarily, and its mechanism was studied, thereby providing a theoretical basis for future clinical studies.

Actinidia chinensis Planch. root extract inhibits the proliferation, migration and invasion of breast cancer cells via the AKT/GSK-3ß signaling pathway.

INTRODUCTION: Actinidia chinensis Planch. root extract (acRoots), known as a traditional Chinese medicine (TCM), has shown antitumor efficacy in various types of human cancers. However, its role and underlying mechanisms in breast cancer (BCa) have not been elucidated. MATERIAL AND METHODS: In the present study, the effects of acRoots on cell viability, apoptosis, migration and invasion were analyzed by MTT assay, colony formation, flow cytometry, wound healing and Transwell assay in MDA-MB-231 and MDA-MB-453 breast cancer cell lines. The expression levels of relevant proteins were determined by Western blot assay. RESULTS: The results revealed that acRoots inhibited proliferation, migration, and invasion and promoted apoptosis of BCa cells. Moreover, acRoots decreased the expression of cyclin D1, survivin, Bcl-2, N-cadherin, and Snail and increased the expression of Bax and E-cadherin in MDA-MB-231 and MDA-MB-453 cells. AcRoots inhibited the AKT/GSK-3b pathway by decreasing the levels of phosphorylated AKT, phosphorylated GSK-3b and b-catenin. CONCLUSIONS: The described effects of acRoots on the cultured BCa cells suggest that they may be mediated by the inhibition of the AKT/GSK-3b signaling pathway. Thus, further studies are warranted to test the possibility that AcRoots may be used as a promising anticancer agent for breast cancer treatment.