| 周佳林,黄雪云,刘翔,等.基于系统药理学探讨半夏-天南星调控铁死亡、细胞自噬和凋亡治疗原发性肝癌的作用机制[J].浙江中医药大学学报,2023,47(9):1087-1099. |
| 基于系统药理学探讨半夏-天南星调控铁死亡、细胞自噬和凋亡治疗原发性肝癌的作用机制 |
| Explore the Mechanism of Pinellia Ternata-Rhizoma Arisaematis in the Treatment of Primary Liver Cancer by Regulating Ferroptosis， Autophagy and Apoptosis Based on Systematic Pharmacology |
| DOI：10.16466/j.issn1005-5509.2023.09.018 |
| 中文关键词: 半夏-天南星 肝癌 铁死亡 细胞凋亡 细胞自噬 作用机制 |
| 英文关键词: Pinellia Ternata-Rhizoma Arisaematis liver cancer ferroptosis apoptosis autophagy mechanism |
| 基金项目:江西省中医药管理局科技计划项目(2022A071)；江西省教育厅科学技术研究项目(GJJ2200944) |
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| 中文摘要: |
| [目的] 运用系统药理学探讨半夏-天南星药对调控铁死亡、细胞自噬和细胞凋亡治疗原发性肝癌的作用机制。[方法] 利用中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP)数据库获取半夏-天南星活性成分和靶点，人类基因综合数据库(Human Gene Comprehensive Database，GeneCards)和基因疾病关联数据库(Gene-Disease Association Database，DisGeNET)获取原发性肝癌靶点，构建“半夏-天南星-化合物-靶点”网络；利用铁死亡数据库(Ferroptosis Database，FerrDb)、人类自噬数据库(Human Autophagy Database，HADb)和GeneCards获取铁死亡、细胞自噬、细胞凋亡的相关基因，将半夏-天南星治疗肝癌的潜在靶点与铁死亡靶点、细胞自噬靶点、细胞凋亡靶点及三者交集靶点分别映射，并分别进行蛋白互作(protein-protein interactions，PPI)网络、基因本体(gene ontology，GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析；利用癌症基因组图谱(the Cancer Genome Atlas，TCGA)数据库分析共有靶点在肝癌组织的表达水平，以及与肝癌分期和预后的关系。[结果] 共得到半夏-天南星核心成分13个，靶点75个，肝癌靶点1 890个，半夏-天南星治疗肝癌的潜在靶点31个，其与铁死亡、细胞自噬、细胞凋亡相关靶点分别有7、11、21个重复靶点，其中丝氨酸/苏氨酸蛋白激酶 1(serine/threonine-protein kinase 1，AKT1)、血管内皮生长因子A(vascular endothelial growth factor A，VEGFA)、细胞肿瘤抗原p53(tumor protein p53，TP53)、转录因子p65(transcription factor p65，TF65/RELA)和低氧诱导因子-1α(hypoxia-inducible factor-1α，HIF-1α)为共有靶点；且其表达水平在肝癌组织中存在差异，也与肝癌分期和预后存在相关性。 [结论] 半夏-天南星可能通过AKT1、VEGFA、TP53、RELA和HIF-1α等靶点调控铁死亡、细胞自噬和细胞凋亡，从而发挥治疗肝癌的作用。 |
| 英文摘要: |
| [Objective] To investigate the mechanism of Pinellia Ternata-Rhizoma Arisaematis in the treatment of primary liver cancer by regulating ferroptosis， autophagy and apoptosis by using systematic pharmacology. [Methods] Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database was used to obtain the active components and targets of Pinellia Ternata-Rhizoma Arisaematis， Human Gene Comprehensive Database(GeneCards) and Gene-Disease Association Database(DisGeNET) were used to obtain the targets of primary liver cancer， and the “Pinellia Ternata-Rhizoma Arisaematis-compound-target” network was constructed. Ferroptosis Database(FerrDb)， Human Autophagy Database(HADb) and GeneCards database were used to obtain the genes related to ferroptosis， autophagy and apoptosis. Protein-protein interactions(PPI)， gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis were performed on the potential targets of Pinellia Ternata-Rhizoma Arisaematis in the treatment of liver cancer and the successful targets mapped by ferroptosis， autophagy， apoptosis and the intersection of the three targets. The expression levels of common targets in liver cancer tissues and their relationship with liver cancer stage and prognosis were analyzed by using the Cancer Genome Atlas(TCGA) database. [Results] A total of 13 core components and 75 target sites of Pinellia Ternata-Rhizoma Arisaematis were obtained， 1 890 target sites of primary liver cancer were obtained， and 31 potential targets of Pinellia Ternata-Rhizoma Arisaematis for the treatment of primary liver cancer were obtained. There were 7，11 and 21 repetitive targets related to ferroptosis， autophagy and apoptosis， respectively. Serine/threonine-protein kinase 1(AKT1)， vascular endothelial growth factor A(VEGFA)， tumor protein p53(TP53)， transcription factor p65(TF65/RELA) and hypoxia-inducible factor-1α(HIF-1α) were the common targets; and the expression level were different in liver cancer tissues， and also correlated with liver cancer stage and prognosis. [Conclusion] Pinellia Ternata-Rhizoma Arisaematis may play a therapeutic role in primary liver cancer by mediating AKT1， VEGFA， TP53， RELA， HIF-1α and other targets to regulate ferroptosis， autophagy and apoptosis. |
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