目的 通过网络药理学及分子对接探究尿石素A治疗结肠癌的主要生物过程和信号通路，阐明其作用机制。方法 通过SwissTargetPrediction、Targets SUP-PRED和Cbligand等数据库预测尿石素A药物潜在作用靶点，检索DisGeNET、OMIM、Gene Cards等数据库获得结肠癌相疾病靶点；通过Venn图获得相关交集靶点。运用STRING数据库构建交集靶点的蛋白相互作用（PPI）网络；使用Cytoscape软件对STRING数据库筛选的靶点进行网络拓扑分析筛选关键靶点；运用David数据库对交集靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析，最后通过分子对接明确尿石素A治疗结肠癌的作用机制。结果 预测得到尿石素A靶点260个，筛选、去重得到结肠癌疾病靶点3 289个，最后得到交集靶点106个。核心靶点21个，得到蛋白激酶B1（Akt1）、表皮生长因子受体（EGFR）、胱天蛋白酶3（CASP3）、雌激素受体1（ESR1）、环加氧酶2（PTGS2）等10个核心靶点。GO和KEGG分析表示，尿石素A可能通过癌症通路、癌症相关蛋白聚糖通路等治疗结肠癌的作用。分子对接结果显示尿石素A与核心靶点对接结合能均小于−6.9 kcal/mol。结论 尿石素A可通过多靶点和多通路的途径发挥治疗结肠癌的功效。

Objective To investigate the main biological processes and signaling pathways of mechanism urolithin A in treatment of colon cancer through network pharmacology and molecular docking, and elucidate its action. Methods To predict the potential targets of urolithin A by SwissTargetPrediction, Targets SUP-PRED, and Cbligand database. To obtain the target information of colon cancer through DisGeNET, OMIM, Gene Cards. The intersection targets of urolithin A and colon cancer were obtained by Venn diagram. PPI network of intersection targets was constructed by STRING database. Perform network topology analysis on the target genes selected from the STRING database using the Cytoscape software to identify key target genes. David database was used to analyze the GO and KEGG pathway analysis of intersection targets. Finally, mechanism of action of urolithin A and key targets was further clarified by molecular docking. Results A total of 260 urolithin A targets were predicted, 3 289 colon cancer disease targets were obtained by screening and deduplication, and 108 intersection targets were finally obtained. Ten core targets were obtained, including protein kinase B1 (Akt1), epidermal growth factor receptor (EGFR), Caspase 3 (CASP3), estrogen receptor 1 (ESR1), and cycloxygenase 2 (PTGS2). GO and KEGG enrichment analysis mainly urolithin A may play a role in treatment of colon cancer through pathways in cancer, proteoglycans in cancer. Results of molecular docking showed that the binding energy of urolithin A to key targets was less than −6.9 kcal/mol. Conclusion Urolithin A may regulate more pathways and more targets to play a role in treatment of colon cancer.

R965

山东省重点研发计划项目(2022TZXD0019);山东省自然科学基金资助项目(ZR2023QH197);山东省高等学校“青创科技计划”团队项目(2019KJM006);枣庄市产学研联合基金项目(2019LHJJ006)