目的:观察珍珠梅改善肝细胞癌(HCC)对顺铂耐药性的疗效,并通过网络药理学预测其作用机制.方法:通过文献检索珍珠梅活性成分,利用Swiss Target Prediction平台预测珍珠梅的靶点,运用Cytoscape 3.7.2软件构建"珍珠梅活性-成分-靶点"网络.在David数据库中对靶点进行KEGG通路富集分析,利用AutoDock Vain将核心靶点与珍珠梅活性成分进行分子对接,并通过CCK-8法检测细胞增殖抑制率,Western Blot分析蛋白表达,构建斑马鱼HepG2细胞异种移植动物模型,检测珍珠梅改善HCC对顺铂耐药性疗效.结果:共筛选出25个交集靶点,关键靶点主要富集在PI3K-AKT信号通路、MAPK信号通路、EGFR酪氨酸激酶抑制剂耐药性通路、MicroRNA in cancer等信号通路.珍珠梅活性成分和核心靶点具有较稳定的结合活性.珍珠梅可通过下调MPR2蛋白表达改善HCC对顺铂的耐药性.结论:珍珠梅可通过降低MRP2蛋白的表达降低HCC对顺铂的敏感性.
Mechanism of Sorbaria sorbifolia in improving cisplatin resistance of hepatocellular carcinoma
Objective:To observe the efficacy of Sorbaria sorbifolia(SS)to ameliorate the efficacy of hepatocellular carcinoma(HCC)against cisplatin resistance,and to predict its mechanism of action by network pharmacology.Methods:The active ingredients of SS were searched in the literature,and the targets of SS were predicted using Swiss Target Prediction platform,and the network of'ingredient of SS-target'was constructed using Cytoscape 3.7.2 software.The targets were analysed in David database(KEGG),and the core targets were molecularly docked with the active ingredients of SS using AutoDock Vain.The cell proliferation inhibition rate was detected by CCK-8 method,and the protein expression was analysed by Western Blot.Construction of zebrafish HepG2 cell xenograft animal model to test the therapeutic efficacy of SS in improving the cisplatin resistance in HCC.Results:A total of 25 common targets were screened,and the key targets were mainly enriched in PI3K-AKT signalling pathway,MAPK signalling pathway,EGFR tyrosine kinase inhibitor resistance pathway,MicroRNA in cancer.The active ingredients of SS and the core targets had more stable binding activities.SS could improve the resistance of HCC to cisplatin by down-regulating MPR2 protein.Conclusion:SS can reduce the sensitivity of HCC to cisplatin by decreasing the expression of MRP2 protein.
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