基于网络药理学和细胞实验探讨Hispolon抗结肠癌的作用机制

Mechanism of Hispolon in treatment of colon cancer based on network pharmacology and cell experiment

目的运用网络药理学预测和细胞实验探讨Hispolon抗结肠癌的作用机制。方法Swiss Target Prediction网站获取Hispolon的潜在靶点,与疾病数据库GeneCards、OMIM中结肠癌靶点取交集;利用STRING11.0数据库构建靶点相互作用网络,使用Cytoscape3.7.2软件挖掘Hispolon作用于结肠癌的核心靶点,通过Metascape数据库进行GO和KEGG富集分析,最后采用Western blot验证Hispolon对结肠癌细胞SW480中部分关键靶点的调控作用。结果筛选出Hispolon抗结肠癌作用靶点69个,核心靶点包括BCL-2L1、EP300、CDK1、AR、MTOR、EGFR;富集分析发现Hispolon通过调节癌症相关通路、PI3K-Akt信号通路、前列腺癌相关通路等发挥抗结肠癌作用,并且通路中关键靶点涉及BCL-2L1、EP300、CDK1、MTOR和EGFR核心靶点。通过细胞实验证实Hispolon可下调靶点蛋白BCL-2L1和mTOR的表达,促进SW480细胞凋亡。结论Hispolon治疗结肠癌,具有多靶点、多通路协同作用的特点,该研究为进一步阐明Hispolon抗结肠癌作用机制及临床应用提供科学依据。

Aim To explore the mechanism of Hispolon in the treatment of colon cancer by network pharmacology and cell experimental validation.Methods The potential targets of Hispolon were obtained from the Swiss Target Prediction website,and intersected with colon cancer targets from GeneCards and OMIM databases.The protein-protein interaction network of targets was built by the STRING11.0 database.Meanwhile,the core targets of PPI network was explored by Cytoscape 3.7.2 software.Furthermore,the GO and KEGG pathway enrichment were analyzed by Metascape database.Finally,Western blotting was used to verify the regulation of Hispolon on some key targets in colon cancer cell SW480.Results Sixty-nine common targets of Hispolon and colon cancer were obtained,which were colon cancer therapeutic targets.The core targets included BCL-2L1,EP300,CDK1,AR,MTOR and EGFR.The enrichment analysis showed that Hispolon played a role in the treatment of colon cancer by regulating the pathways in cancer,PI3K-Akt signaling pathway,prostate cancer and MicroRNAs in cancer.And the key targets in the pathway involved core targets such as BCL-2L1,EP300,CDK1,MTOR and EGFR.Cell experiments confirmed that Hispolon promoted SW480 cell apoptosis by down-regulating the expression of target proteins BCL-2L1 and mTOR.Conclusions The discussion of the molecular mechanism of Hispolon in the treatment of colon cancer suggests that Hispolon may play a role in the treatment of colon cancer through multiple targets and multiple pathways.The results provide a scientific basis for the elucidation of the mechanisms and clinical application of Hispolon against colon cancer.