基于网络药理学和分子对接探究二氢杨梅素调脂抗肝癌的作用

目的探讨miR-203a-3p通过ALOX15途径调控胃癌细胞铁死亡的机制。 方法检测胃癌组织和癌旁正常组织的铁死亡指标——活性氧诱导脂质过氧化(lipid-ROS)水平。对胃癌组织miR-203a-3p与lipid-ROS进行Pearson相关性分析。在胃正常细胞和胃癌细胞株中过表达或敲低相关分子后,检测其lipid-ROS和线粒体膜电位(MMP)。 结果miR-203a-3p水平胃癌组织高于癌旁正常组织,胃癌细胞株高于胃正常细胞；lipid-ROS水平胃癌组织低于癌旁正常组织,胃癌细胞株低于胃正常细胞(P＜0.05)。在胃癌组织中,miR-203a-3p与lipid-ROS呈负相关(P＜0.05)。胃癌组织ALOX15 mRNA低于癌旁正常组织(P＜0.05)。过表达miR-203a-3p后,胃正常细胞lipid-ROS、胃癌细胞MMP、所有细胞ALOX15 mRNA和蛋白水平降低；敲低miR-203a-3p后,胃癌细胞lipid-ROS、所有细胞ALOX15 mRNA和蛋白升高；敲低ALOX15时胃正常细胞lipid-ROS和胃癌细胞MMP降低,过表达ALOX15后胃癌细胞lipid-ROS升高(P＜0.05)。 结论胃癌细胞高表达的miR-203a-3p可靶向ALOX15,减少ALOX15表达,抑制其铁死亡发生。

Exploring the effect of dihydromyricetin in regulating lipid metabolism against liver cancer based on network pharmacology and molecular docking

To explore the effects of dihydromyricetin in regulating lipid metabolism against liver cancer based on network pharmacology and molecular docking methods. MethodsSwissTarget, TargetNet and TCMSP databases were used to predict the potential targets of dihydromyricetin, and GeneCards, OMIM and TTD databases were used to obtain the related genes of liver cancer and lipid metabolism. Venny 2.1.0 was used to obtain the relevant targets of dihydromyricetin for lipid metabolism regulation against liver cancer, STRING database and Cytoscape software were used to visualize and analyze the relevant target interaction network. Rstudio software was used for GO and KEGG enrichment analysis of related targets, and PyMol 2.5.1 and Autodock Vina software were used for molecular docking validation of core target genes. Results179 dihydromyricetin action targets, 427 genes related to lipid metabolism and 1 246 genes related to liver cancer were obtained. Dihydromyricetin has 15 potential targets and 9 core target genes, mainly involved in ovarian steroidogenesis, steroid hormone biosynthesis, chemical carcinogenesis-receptor activation and other pathways. The binding energy results of the core target genes with dihydromyricetin had good binding properties. ConclusionDihydromyricetin may exert its lipid metabolism regulating and anti-liver cancer effect by affecting biological processes and regulating key pathways through acting on nine core targets.