整合网络药理学与实验验证探索芦荟素抗胃癌的药理机制。

PURPOSE: This study was designed to evaluate the pharmacological mechanisms of Aloin against gastric cancer (GC) via network pharmacology analysis combined with experimental verification. METHODS: Using network pharmacology methods, the potential targets of Aloin and targets related to GC were screened from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the core targets and pathways of Aloin against GC. The expressions of major targets predicted by network pharmacology in normal stomach tissues and GC tissues and their relationships with overall survival of GC were searched in GEPIA, HPA and DriverDBv3 database. The results of 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 AKT1 and CASP3, were hub genes. GO enrichment analysis involved 93 biological processes, 19 cellular components, and 37 molecular functions. KEGG enrichment analysis indicated that the anti-cancer effect of Aloin was mediated through multiple pathways, such as PI3K-AKT, FoxO and Ras signaling pathway. Among them, the PI3K-AKT signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of GC. The validation of key targets in GEPIA, HPA and DriverDBv3 database showed that the verification results for most core genes were consistent with this study. Then, the results of in vitro experiment indicated that Aloin could inhibit proliferation of NCI-N87 cells and induce cell apoptosis. The results also showed that Aloin could decrease the mRNA and protein expressions of PI3K and AKT, suggesting that Aloin can treat GC by inducing cell apoptosis and regulating the PI3K-AKT signaling pathway. CONCLUSION: This study identified the potential targets of Aloin against GC using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Aloin in treatment of GC.

目的：本研究旨在通过网络药理学分析结合实验验证，评估芦荟素对胃癌（GC）的药理机制。

方法：利用网络药理学方法，从公共数据库中筛选出芦荟素的潜在靶点和与 GC 相关的靶点。对蛋白-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，预测芦荟素治疗 GC 的核心靶点和通路。在 GEPIA、HPA 和 DriverDBv3 数据库中搜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 总生存的关系。通过体外实验验证网络药理学分析的结果。

结果：通过搜索芦荟素和 GC 靶点的交集，共检索到 129 个潜在靶点。PPI 网络分析表明，AKT1 和 CASP3 等 10 个靶标为枢纽基因。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，芦荟素的抗癌作用是通过多种途径介导的，如 PI3K-AKT、FoxO 和 Ras 信号通路。其中，PI3K-AKT 信号通路富集的基因数量最多，可能在 GC 治疗中发挥更大作用。在 GEPIA、HPA 和 DriverDBv3 数据库中对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。然后，体外实验结果表明，芦荟素可以抑制 NCI-N87 细胞的增殖并诱导细胞凋亡。结果还表明，芦荟素可以降低 PI3K 和 AKT 的 mRNA 和蛋白表达，提示芦荟素可以通过诱导细胞凋亡和调节 PI3K-AKT 信号通路来治疗 GC。

结论：本研究通过网络药理学和体外验证鉴定了芦荟素治疗 GC 的潜在靶点，为芦荟素治疗 GC 的药理机制提供了新的认识。