关键词: 高良姜, 胃癌, 网络药理学, 分子对接, 作用机制

Abstract:

This study aims to reveal the active components and mechanism of action of Alpinia officinarum Hance in the treatment of gastric cancer using network pharmacology and in vitro experimental validation. Acquisition of active ingredients and their targets of action of A. officinarum with the help of Traditional Chinese Medicine Systematic Pharmacology Platform(TSMSP). Disease targets for gastric cancer were obtained from GeneCards, OMIM, and DisGeNET databases, and then potential active ingredients, core targets, and associations between pathways were analyzed by Venny 2.1.0, Cytoscape 3.9.1, DAVID, and STRING databases for the treatment of gastric cancer with A. officinarum. Molecular docking was performed using AutoDock Vina software. Finally, validated by in vitro experiments with human gastric adenocarcinoma AGS cells. The results of network pharmacology showed that the active ingredients of A. officinarum in the treatment of gastric cancer may be galangin, isorhamnetin, kaempferol, medetanin, quercetin. The key targets may be estrogen receptor 1 (ESR1), proto-oncogene tyrosine-protein kinase SRC (SRC), protein kinase B1 (AKT1), Caspase-3 (CASP3), etc., which are mainly enriched in signaling pathways such as pathways in cancer, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and MicroRNAs in cancer. The molecular docking results showed that galangin has a strong binding ability to the key targets. The results of in vitro experiments showed that the inhibitory effect of galangin on AGS cells was enhanced with the increase of the drug dose concentration, showing a significant dose-effect dependence relationship. The healing rate of cell scratches in the different concentrations of galangin administration groups was concentration dependent, with the higher concentration resulting in a lower healing rate. Galangin downregulated the protein of phosphorylated protein kinase B (p-AKT), SRC and prostaglandin-endoperoxide synthase 2 (PTGS2) and the mRNA expression of V-Myc avian myelocytomatosis viral oncogene homolog (MYC), PTGS2, epidermal growth factor (EGF), and vascular endothelial growth factor A (VEGFA), and upregulated the protein of tumor protein 53 (P53) and the mRNA expression of TP53 and jun proto-oncogene (JUN) in AGS cells. The intervention of A. officinarum in gastric cancer is characterized by multi-targets and multi-pathways. Among them, the active ingredient galangin can significantly inhibit the viability of AGS cells, and its mechanism of action may be related to the promotion of P53/JUN and the inhibition of PI3K/AKT pathway.

Key words: Alpinia officinarum Hance, gastric cancer, network pharmacology, molecular docking, mechanism