Wang Xinmiao, Cao Luchang, Wu Jingyuan, Zhu Guanghui, Zhu Xiaoyu, Zhang Xiaoxiao, Han Duoduo, Shui Ning, Ni Baoyi, Li Jie
Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
Beijing University of Traditional Chinese Medicine, Beijing 100029, China.
Evid Based Complement Alternat Med. 2021 Nov 29;2021:5773802. doi: 10.1155/2021/5773802. eCollection 2021.
Arsenic trioxide (, Pishi, arsenolite, AsO, and CAS 1327-53-3), a naturally occurring and toxic mineral as a drug for more than 2000 years in China, has been found to have a valuable function in hepatocellular carcinoma (HCC) in recent years. However, its exact mechanism remains to be elucidated. Therefore, this study was intended to explore the potential anti-HCC mechanism of arsenic trioxide through network pharmacology.
The potential targets of arsenic trioxide were collected from PubChem and TargetNet. HCC targets were obtained from the GeneCards database. Then, a protein-protein interaction (PPI) network of arsenic trioxide and HCC common targets was established using STRING. GO and KEGG pathway enrichment analyses were performed by the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Finally, an arsenic trioxide-target-pathway-HCC network was built by Cytoscape 3.2.1, and network topological analysis was carried out to screen the key candidate targets.
A total of 346 corresponding targets of arsenic trioxide and 521 HCC-related targets were collected. After target mapping, a total of 52 common targets were obtained. GO analysis showed that the biological process was mainly involved in the negative regulation of cellular senescence, response to tumor necrosis factor, and cellular response to hypoxia. Molecular functions included NF-kappa B binding, enzyme binding, p53 binding, and transcription factor binding. Cellular components mainly were replication fork, ESC/E(Z) complex, RNA polymerase II transcription factor complex, and organelle membrane. KEGG pathways were mainly enriched in the PI3K-Akt signaling pathway, VEGF signaling pathway, p53 signaling pathway, HIF-1 signaling pathway, TNF signaling pathway, AMPK signaling pathway, NF-kappa B signaling pathway, FoxO signaling pathway, ErbB signaling pathway, and MAPK signaling pathway. In the arsenic trioxide-target-pathway-HCC network, targets such as AKT1, RAF1, RELA, TP53, and PTEN had a higher degree. Our study showed that key targets of arsenic trioxide were mainly involved in multiple biological processes and pathways. It provided a theoretical basis for the screening of drug targets.
三氧化二砷（砒石、白砒、As₂O₃，化学物质登记号1327 - 53 - 3）是一种天然存在的有毒矿物质，在中国作为药物使用已有2000多年历史，近年来发现其在肝细胞癌（HCC）中具有重要作用。然而，其确切机制仍有待阐明。因此，本研究旨在通过网络药理学探索三氧化二砷潜在的抗肝癌机制。
从PubChem和TargetNet收集三氧化二砷的潜在靶点。从GeneCards数据库获取肝癌靶点。然后，使用STRING构建三氧化二砷与肝癌共同靶点的蛋白质 - 蛋白质相互作用（PPI）网络。通过注释、可视化和综合发现数据库（DAVID）进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。最后，用Cytoscape 3.2.1构建三氧化二砷 - 靶点 - 通路 - 肝癌网络，并进行网络拓扑分析以筛选关键候选靶点。
共收集到三氧化二砷的346个相应靶点和521个与肝癌相关的靶点。经过靶点映射，共获得52个共同靶点。GO分析表明，生物学过程主要涉及细胞衰老的负调控、对肿瘤坏死因子的反应以及细胞对缺氧的反应。分子功能包括NF - κB结合、酶结合、p53结合和转录因子结合。细胞成分主要是复制叉、ESC/E(Z)复合体、RNA聚合酶II转录因子复合体和细胞器膜。KEGG通路主要富集在PI3K - Akt信号通路、VEGF信号通路、p53信号通路、HIF - 1信号通路、TNF信号通路、AMPK信号通路、NF - κB信号通路、FoxO信号通路、ErbB信号通路和MAPK信号通路。在三氧化二砷 - 靶点 - 通路 - 肝癌网络中，AKT1、RAF1、RELA、TP53和PTEN等靶点的度数较高。我们的研究表明，三氧化二砷的关键靶点主要参与多种生物学过程和通路。这为药物靶点的筛选提供了理论依据。
