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

Yanan Pang1, Zhiyong Liu1, Shanrong Liu2

  • 1Department of Laboratory Diagnostics, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.

Pathology Oncology Research : POR
|December 4, 2018
PubMed

Insights

Arsenic trioxide shows anti-cancer effects beyond leukemia. This study identifies key molecular targets and pathways, including the PI3K-Akt pathway, suggesting new therapeutic strategies for pancreatic cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Arsenic trioxide is approved for acute promyelocytic leukemia (APL).
  • Emerging evidence suggests broader anti-cancer roles in various malignancies.
  • The precise molecular mechanisms underlying its anti-cancer activity remain incompletely understood.

Purpose of the Study:

  • To systematically explore the direct protein targets (DPTs) of arsenic trioxide.
  • To elucidate the interaction network of DPTs and associated genes.
  • To identify potential therapeutic targets for arsenic trioxide in cancer treatment.

Main Methods:

  • Utilized public databases like DrugBank (DB) and STRING for target identification.
  • Performed systematic network analysis of identified targets and associated genes.
  • Conducted enrichment analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.
  • Investigated gene alternations in pancreatic cancer using the cBio portal.

Main Results:

  • Identified seven direct protein targets (DPTs) and 111 DPT-associated genes.
  • Revealed 10 KEGG pathways associated with arsenic trioxide's action.
  • Highlighted the phosphatidylinositol-4,5-bisphosphate-3-kinase -Akt (PI3K-Akt) pathway and pancreatic cancer pathway as highly correlated, sharing five targets.
  • Observed significant gene alternations in pancreatic cancer for selected critical genes.

Conclusions:

  • Arsenic trioxide exhibits anti-tumor functions potentially mediated through the PI3K-Akt signaling pathway.
  • The identified critical genes represent potential therapeutic targets for pancreatic cancer treatment.
  • Further research into arsenic trioxide's molecular mechanisms could lead to novel cancer therapies.
Keywords:
Arsenic trioxideBioinformatics analysisGenes/proteins interactionPancreatic cancer

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