Identification of Key Potential Targets and Pathway for Arsenic Trioxide by Systemic Bioinformatics Analysis in Pancreatic Cancer.

Abstract

Arsenic trioxide is an approved chemotheraputic agent for the treatment of acute promyelocytic leukemia (APL). Recently, numerous studies suggested that arsenic trioxide acts as anti-cancer roles in various human malignancies. However, the molecular mechanisms are not fully elucidated. In this study, we explored the critical targets of arsenic trioxide and their interaction network systematically by searching the publicly available published database like DrugBank (DB) and STRING. Seven direct protein targets (DPTs) and 111 DPT-associated genes were identified. The enrichment analysis of arsenic trioxide associated genes/proteins revealed 10 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Among these pathways, phosphatidylinositol-4,5-bisphosphate-3-kinase -Akt (PI3K-Akt) single pathway and pancreatic cancer pathway are highly correlated with arsenic trioxide and have 5 overlapped targets. Then we investigated the gene alternation of selected critical genes in pancreatic cancer studies using cBio portal. These results indicated that arsenic trioxide could act anti-tumor function through PI3K-Akt single pathway and identified critical genes might be therapeutic targets for pancreatic cancer.