摘要
目的:基于网络药理学方法,系统探讨苏木酮A(SA)治疗结直肠腺癌(COAD)的潜在作用机制。方法:通过SwissTargetPrediction、GeneCards、OMIM、DisGeNET等数据库筛选SA及COAD相关靶点,取交集并进行GO与KEGG通路富集分析;利用STRING和Cytoscape构建蛋白互作(PPI)网络并筛选核心靶点;结合分子对接分析SA与关键蛋白的结合活性;通过GEPIA数据库分析关键基因的表达及与患者总体生存率的关系;并通过CCK-8实验验证SA对Caco-2细胞增殖的影响。结果:共筛选出125个潜在作用靶点及3 791个COAD相关靶点,交集分析获得若干候选靶点。GO与KEGG分析显示,相关靶点主要富集于细胞信号转导、PI3K-Akt、MAPK、Ras等与肿瘤发生密切相关的通路。PPI网络分析筛选出MTOR、SRC、EGFR、BCL2、ESR1 5个核心靶点。分子对接结果表明SA与SRC、EGFR结合能力最强。GEPIA分析发现,SRC高表达与不良预后相关,而BCL2低表达与不良预后相关。CCK-8实验进一步证实SA对Caco-2细胞具有显著的浓度依赖性抑制作用。结论:SA可能通过调控SRC、EGFR、BCL2等关键靶点,干预PI3K-Akt、MAPK等通路,抑制COAD细胞增殖并促进凋亡,从而发挥抗肿瘤作用。本研究为SA在COAD治疗中的潜在应用提供了理论依据,并为天然产物的抗肿瘤研究提供了新的思路。
Objective:To systematically explore the potential mechanisms of Sappanone A(SA)in the treatment of colon rectal adenocarcinoma(COAD)using a network pharmacology approach.Methods:Potential targets of SA and COAD-related genes were obtained from SwissTargetPrediction,GeneCards,OMIM,and DisGeNET databases.The overlapping genes were subjected to GO and KEGG enrichment analyses.A protein-protein interaction(PPI)network was constructed using STRING and visualized in Cytoscape to identify core targets.Molecular docking was performed to evaluate the binding activity between SA and key proteins.GEPIA was employed to analyze the expression profiles and prognostic significance of core genes.Furthermore,a CCK-8 assay was used to assess the inhibitory effect of SA on the proliferation of Caco-2 cells.Results:A total of 125 potential targets of SA and 3791 COAD-related genes were identified,with several overlapping genes obtained.GO and KEGG analyses revealed enrichment in pathways related to signal transduction,PI3K-Akt,MAPK,and Ras signaling.Five core targets—MTOR,SRC,EGFR,BCL2,and ESR1—were screened from the PPI network.Molecular docking indicated that SA had the strongest binding affinity with SRC and EGFR.GEPIA analysis showed that high SRC expression was associated with poor prognosis,while low BCL2 expression correlated with unfavorable outcomes.CCK-8 assays confirmed that SA inhibited Caco-2 cell proliferation in a dose-dependent manner.Conclusion:SA may exert anti-COAD effects by modulating key targets such as SRC,EGFR,and BCL2,thereby regulating PI3K-Akt and MAPK pathways,inhibiting proliferation,and promoting apoptosis.This study provides a theoretical basis for the potential application of SA in COAD treatment and offers new insights into the anticancer mechanisms of natural products.
作者
王毅军
王剑
WANG Yijun;WANG Jian(Department of Gastrointestinal Surgery,Xiangzhou District People’s Hospital,Xiangyang 441100,Hubei,China)
出处
《医学理论与实践》
2026年第6期923-928,共6页
The Journal of Medical Theory and Practice
关键词
结直肠腺癌
苏木酮A
网络药理学
Colon rectal adenocarcinoma
Sappanone A
Network pharmacology
