网络药理学与实验验证结合探究芦荟素抗胃癌的药理机制

Network Pharmacology and Experimental Validation Were Combined to Explore the Pharmacological Mechanism of Aloe against Gastric Cancer

摘要: 目的：本研究旨在通过网络药理学分析结合实验验证来评价芦荟素对胃癌(GC)的药理作用。方法：采用网络药理学方法，从公共数据库中筛选出芦荟因的潜在靶点和GC相关靶点。采用蛋白–蛋白相互作用(PPI)网络、基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析，预测芦荟因针对GC的核心靶点和通路。在GEPIA、HPA和DriverDBv3数据库中检索网络药理学预测的主要靶点在正常胃组织和GC组织中的表达及其与GC总生存期的关系。通过体外实验验证了网络药理学分析结果。结果：通过搜索Aloin和GC目标的交叉点，共检索到129个潜在目标。PPI网络分析表明，AKT1和CASP3等10个靶点为枢纽基因。GO富集分析涉及93个生物过程、19个细胞成分和37个分子功能。KEGG富集分析表明，芦荟因的抗癌作用是通过PI3K-AKT、FoxO和Ras信号通路等多种途径介导的。其中，含有最多富集基因的PI3K-AKT信号通路可能在GC的治疗中发挥更大的作用。GEPIA、HPA和DriverDBv3数据库中关键靶点的验证表明，大多数核心基因的验证结果与本研究一致。体外实验结果表明，芦荟素可抑制NCI-N87细胞增殖，诱导细胞凋亡。结果：芦荟因可降低PI3K和AKT的mRNA和蛋白表达，表明芦荟因可以通过诱导细胞凋亡和调节PI3K-AKT信号通路来治疗GC。

Abstract: This study aims to evaluate the pharmacological effect of aloe on gastric cancer (GC) through network pharmacological analysis combined with experimental verification. Methods: The potential targets of aloe cause and GC related targets were selected from public databases. Protein-protein interaction (PPI) network, Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway enrichment analysis were used to predict the core targets and pathways of GC. The expression of the main targets of the network pharmacology in normal gastric and GC tissues and their relationship with GC overall survival. The results of the network pharmacology analysis were verified by in vitro experiments. Results: A total of 129 potential targets were retrieved by searching the intersection of Aloin and GC targets. PPI network analysis indicated that 10 targets including AKT 1 and CASP 3 are hub genes. The GO enrichment analysis involved 93 biological processes, 19 cellular components, and 37 molecular functions. KEGG enrichment analysis indicated that the anticancer effects of aloe cause are mediated through several pathways including PI3K-AKT, FoxO and Ras signaling pathways. Among these, the PI3K-AKT signaling pathway, which contains the most enriched genes, may play a greater role in the treatment of GC. The validation of key targets in the GEPIA, HPA and DriverDBv3 databases showed that the validation of most core genes is consistent with this study. In vitro results showed that Averin inhibited cell proliferation and induced apoptosis in NCI-N87 cells. Conclusion: Aloe reduced the mRNA and protein expression of PI3K and AKT, indicating GC by inducing apoptosis and regulating PI3K-AKT signaling.