Sun Jinpeng, Qi Xinmeng, Yang Cuiyuan, Wang Shanpeng, Jiang Jingwen, Wang Lijie, Song Jiacheng, Yu Bin, Sun Min
College of Integrative Chinese and Western Medicine, Jining Medical University, Jining, Shandong, 272067, People's Republic of China.
Drug Des Devel Ther. 2025 Apr 16;19:2959-2977. doi: 10.2147/DDDT.S492033. eCollection 2025.
To examine the roles and mechanisms of tanshinone IIA (Tan-IIA) in colorectal cancer (CRC) using network pharmacology, molecular docking, and in vitro experiments.
In network pharmacology studies, Tan-IIA targets for treating CRC were identified using public databases. Employing the protein-protein interaction (PPI) network, gene ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the core genes and mechanisms of action of Tan-IIA were obtained. Core targets were validated using Gene Expression Profiling Interactive Analysis, the Human Protein Atlas, DriverDBv3, cBioPortal, and the Tumor Immune Estimation Resource database. Molecular docking validates the binding affinity of Tan-IIA to some key targets. Network pharmacology and molecular docking results were validated via in vitro experiments.
Intersecting Tan-IIA and CRC targets led to the identification of 25 potential targets. PPI analysis identified 10 core targets of Tan-IIA for CRC treatment. Database validation revealed that these core targets were expressed at varying levels in both normal and cancer tissues. Their expression could influence patient prognosis and immune cell infiltration levels. GO analysis revealed 170 biological processes, 42 cellular components, and 83 molecular functions. KEGG analysis indicated that Tan-IIA affected CRC through multiple pathways, including the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), cAMP, and TNF signaling pathways, with the PI3K/AKT pathway being the most enriched. Molecular docking results indicated that Tan-IIA effectively binds to PI3K, AKT, and other partial core targets. In vitro experiments revealed that Tan-IIA suppressed the multiplication and migration of HCT116 and SW480 cells, induced apoptosis, and reduced the PI3K/AKT pathway indicator protein expression, which was reversed by the PI3K/AKT pathway agonist insulin-like growth factor-1.
Network pharmacology, molecular docking, and in vitro validation confirmed that Tan-IIA contributes to CRC treatment through the PI3K/AKT pathway, providing theoretical and experimental foundations for its potential clinical application.
运用网络药理学、分子对接及体外实验，研究丹参酮IIA（Tan-IIA）在结直肠癌（CRC）中的作用及机制。
在网络药理学研究中，利用公共数据库确定Tan-IIA治疗CRC的靶点。通过蛋白质-蛋白质相互作用（PPI）网络、基因本体论（GO）富集分析和京都基因与基因组百科全书（KEGG）通路分析，获得Tan-IIA的核心基因及作用机制。利用基因表达谱交互分析、人类蛋白质图谱、DriverDBv3、cBioPortal和肿瘤免疫评估资源数据库对核心靶点进行验证。分子对接验证Tan-IIA与部分关键靶点的结合亲和力。通过体外实验验证网络药理学和分子对接结果。
Tan-IIA与CRC靶点交叉分析确定了25个潜在靶点。PPI分析确定了Tan-IIA治疗CRC的10个核心靶点。数据库验证显示，这些核心靶点在正常组织和癌组织中均有不同程度的表达。它们的表达可影响患者预后及免疫细胞浸润水平。GO分析揭示了170个生物学过程、42个细胞成分和83个分子功能。KEGG分析表明，Tan-IIA通过多种途径影响CRC，包括磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）、环磷酸腺苷（cAMP）和肿瘤坏死因子（TNF）信号通路，其中PI3K/AKT通路富集程度最高。分子对接结果表明，Tan-IIA能有效结合PI3K、AKT等部分核心靶点。体外实验表明，Tan-IIA抑制HCT116和SW480细胞的增殖和迁移，诱导细胞凋亡，并降低PI3K/AKT通路指示蛋白的表达，而PI3K/AKT通路激动剂胰岛素样生长因子-1可逆转这一作用。
网络药理学、分子对接及体外验证证实，Tan-IIA通过PI3K/AKT通路对CRC治疗有作用，为其潜在临床应用提供了理论和实验基础。
