Evaluation of plasticizer toxicity effects and mechanisms in gastric cancer based on network toxicology and molecular...

Area of Science:

• Environmental Health
• Toxicology
• Molecular Biology

Background:

• Plasticizers, such as dibutyl phthalate (DBP) and diethyl phthalate (DEP), are common environmental pollutants.
• Their potential role in inducing gastric cancer and the underlying molecular mechanisms remain incompletely understood.

Purpose of the Study:

• To investigate the molecular mechanisms of gastric cancer induced by DBP and DEP exposure using network toxicology.
• To identify potential molecular targets and pathways involved in plasticizer-induced toxicity.

Main Methods:

• Network toxicology approach integrating multiple databases (PharmMapper, SwissTargetPrediction, GeneCards, OMIM, DrugBank, TTD).
• Identification of 143 relevant targets and construction of a network diagram.
• Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.
• Protein-protein interaction (PPI) network analysis (cytoHubba).
• Molecular docking to assess binding affinity of plasticizers with key targets.

Main Results:

• 143 potential molecular targets were identified, with 10 central genes including AKT1, GRB2, EGFR, HRAS, JAK2, PIK3CG, PIK3CD, PIK3R1, PTPN11, and SRC.
• Analysis revealed involvement of pathways such as 'Pathways in Cancer', 'Ras signaling pathway', and 'MAPK signaling pathway'.
• Molecular docking confirmed strong binding affinity between DBP/DEP and PIK3CG, PIK3CD, JAK2, HRAS, and PTPN11.

Conclusions:

• Plasticizer exposure, specifically DBP and DEP, may act as an environmental trigger for gastric cancer development.
• Network toxicology provides a valuable framework for understanding the toxicity of environmental pollutants.
• Identified molecular targets and pathways offer potential avenues for further research and intervention.