Exploring the Mechanisms of Arsenic Trioxide (Pishuang) in Hepatocellular Carcinoma Based on Network Pharmacology

Xinmiao Wang; Luchang Cao; Jingyuan Wu; Guanghui Zhu; Xiaoyu Zhu; Xiaoxiao Zhang; Duoduo Han; Ning Shui; Baoyi Ni; Jie Li

doi:10.1155/2021/5773802

Exploring the Mechanisms of Arsenic Trioxide (Pishuang) in Hepatocellular Carcinoma Based on Network Pharmacology

Evid Based Complement Alternat Med. 2021 Nov 29:2021:5773802. doi: 10.1155/2021/5773802. eCollection 2021.

Authors

Xinmiao Wang¹, Luchang Cao¹, Jingyuan Wu^{1

2}, Guanghui Zhu^{1

2}, Xiaoyu Zhu¹, Xiaoxiao Zhang¹, Duoduo Han¹, Ning Shui¹, Baoyi Ni¹, Jie Li¹

Affiliations

¹ Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
² Beijing University of Traditional Chinese Medicine, Beijing 100029, China.

Abstract

Objective: Arsenic trioxide (Pishuang, Pishi, arsenolite, As₂O₃, 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.

Methods: 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.

Results: 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. Conclusions. 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.