基于网络药理学和细胞功能实验探究石榴治疗胃癌的分子药理作用机制OA

Objective To investigate the mechanism underlying the therapeutic effects against gastric cancer based on network pharmacology and cell function assays.Methods The active components of pomegranate and their putative targets were collected from the TCMSP and Herb2.0 databases.Gastric cancer-related targets were obtained from OMIM,TTD,and GeneCards databases,and the intersection between pomegranate-related targets and gastric cancer-related targets was used to identify shared targets.A PPI network was constructed using STRING and Cytoscape,and key targets were screened with CytoNCA.GO and KEGG enrichment analyses were performed using the DAVID database and visualized on the OmicShare platform.Molecular docking was conducted with AutoDock and visualized using PyMOL.For cellular experiments,cell viability was assessed by CCK-8,proliferation by colony formation assay,cell morphology by bright-field imaging,and protein expression by Western blotting.Results Eight active components of pomegranate were identified,along with 225 potential targets.A total of 1,795 gastric cancer-related targets were collected,yielding 122 intersecting targets.GO enrichment yielded 289 terms,involving hormone response and regulation of apoptosis,among others.KEGG enrichment identified 133 pathways,including PI3K/AKT and MAPK/ERK signaling.The PPI network comprised 122 nodes and 1,018 edges,and four key targets were screened:IL-6,EGFR,TP53,and AKT1.CCK-8 assays showed that pomegranate inhibited the viability of HGC-27 and AGS cells in a dose-dependent manner(for instance,after 24-hour treatment with 50 mg/mL,the cell viability was 11%and 46%of the control group,respectively,both P<0.001).Colony formation assays indicated HGC-27 and AGS cells reduced proliferative ability.Western blotting showed downregulation of Bcl-2,p-AKT,and p-ERK expression,upregulation of Bax and PARP(all P<0.05),and no significant changes in pan-AKT and pan-ERK expression(all P<0.05).Conclusion Pomegranate can inhibit the growth and proliferative activity of gastric cancer cells by regulating signaling pathways such as PI3K/AKT and MAPK/ERK,thereby exerting therapeutic effects against gastric cancer.