基于网络药理学和实验验证探讨华蟾素注射液治疗结直肠癌的作用机制

Study on the mechanism of cinobufagin injection in the treatment of colorectal cancer based on network pharmacology and experimental verification

目的探讨华蟾素注射液(cinobufotalin injection,Cino)治疗结直肠癌(colorectal cancer,CRC)的作用机制,并通过体外实验进行初步验证。方法采用网络药理学的方法,筛选出Cino治疗CRC的通路,并利用体外实验进一步验证Cino对CRC细胞HCT-116和CT-26的作用机制。结果利用文献检索出Cino的有效成分共52个,治疗CRC的潜在靶点共70个,KEGG通路富集分析发现,Cino通过EGFR-PI3K-AKT、HIF-1、TNF、IL-17等通路作用于CRC。体外研究发现,Cino能够显著抑制HCT-116和CT-26细胞的活力、集落形成能力、迁移能力,并能够抑制EGFR-PI3K-AKT通路上相关蛋白的表达。结论Cino具有多种成分、多个靶点和多条途径的作用特点,能够抑制CRC细胞的生长,且抑制EGFR-PI3K-AKT信号通路的活化可能是其重要的作用机制。

Objective To explore the mechanism of cinobufagin injection(Cino)in the treatment of colorectal cancer(CRC)and to verify it in vitro.Methods The pathway of Cino in the treatment of CRC was screened by the method of network pharmacology,and the mechanism of Cino on CRC cells HCT-116 and CT-26 was further verified by in vitro experiments.Results A total of 52 active components of Cino and 70 potential targets for the treatment of CRC were found by literatures.KEGG analysis showed that Cino acted on CRC through EGFR-PI3K-AKT,HIF-1,TNF,IL-17 and other pathway.In vitro studies showed that Cino could significantly inhibit the viability,colony forming ability and migration ability of HCT-116 and CT-26 cells,and inhibit the expression of related proteins in EGFR-PI3K-AKT pathway.Conclusion Cino has the action characteristics of multiple components,multiple targets and multiple pathways,which can inhibit the growth of CRC cells,and inhibiting the activation of EGFR-PI3K-AKT signal pathway may be an important mechanism of Cino.