Yin Ting, Wang Hao, Zou Yaqin
1Department of Medicine Linfen Vocational and Technical College, Linfen City, Shanxi 041000, China.
2Department of Stomatology Affiliated Hospital of Guangdong Medical University Zhanjiang City, Guangdong Province, 524001, China.
Acta Pharm. 2025 Apr 10;75(1):41-68. doi: 10.2478/acph-2025-0005. Print 2025 Mar 1.
Oleanolic acid (OA) has demonstrated anticancer effects across various cancers, with some derivatives advancing to clinical trials. Howe ver, its precise mechanisms of action remain unclear, especially in oral squamous cell carcinoma (OSCC). This study employed network pharmacology, bioinformatics, molecular docking, dynamics simulations, and experimental validation to explore OA's anticancer effects in OSCC and elucidate its mechanism of action. OA's pharmacokinetic and physicochemical properties were assessed using SwissADME and Molsoft, revealing high oral bioavailability and GI absorption. SwissTargetPrediction and SuperPred identified protein targets, whereas GeneCards provided OSCC-related targets. A Venn diagram showed 34 overlapping targets between OA and OSCC. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network with 32 nodes and 164 edges, identifying HSP90AA1, STAT3, HSP90AB1, PI3KR1, and NFKB1 as key hub genes. Gene ontology and KEGG enrichment analyses highlighted relevant biological processes, molecular functions, and pathways. Molecular docking and dynamics simulations confirmed the strong binding of OA to hub targets. Experimental validation showed that OA inhibited cell viability and colony formation in a dose-dependent manner, induced apoptosis, and downregulated HSP90AA1, STAT3, and PI3KR1 proteins. In conclusion, this comprehensive study combining network pharmacology, bioinformatics, molecular simulations, and experimental assays provides valuable insights into OA's anticancer potential and detailed mechanism of action in OSCC.
齐墩果酸（OA）已在多种癌症中显示出抗癌作用，其一些衍生物已进入临床试验阶段。然而，其确切的作用机制仍不清楚，尤其是在口腔鳞状细胞癌（OSCC）中。本研究采用网络药理学、生物信息学、分子对接、动力学模拟和实验验证等方法，探讨OA在OSCC中的抗癌作用并阐明其作用机制。使用SwissADME和Molsoft评估OA的药代动力学和理化性质，结果显示其口服生物利用度高且胃肠道吸收良好。通过SwissTargetPrediction和SuperPred确定蛋白质靶点，而GeneCards提供与OSCC相关的靶点。维恩图显示OA和OSCC之间有34个重叠靶点。利用STRING和Cytoscape构建了一个包含32个节点和164条边的蛋白质-蛋白质相互作用（PPI）网络，确定HSP90AA1、STAT3、HSP90AB1、PI3KR1和NFKB1为关键枢纽基因。基因本体论和KEGG富集分析突出了相关的生物学过程、分子功能和信号通路。分子对接和动力学模拟证实OA与枢纽靶点有很强的结合力。实验验证表明，OA以剂量依赖性方式抑制细胞活力和集落形成，诱导细胞凋亡，并下调HSP90AA1、STAT3和PI3KR1蛋白。总之，这项结合网络药理学、生物信息学、分子模拟和实验分析的综合性研究，为OA在OSCC中的抗癌潜力和详细作用机制提供了有价值的见解。
