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

The hypothesized toxicity and potential molecular mechanism of gastric cancer induced by exposure of two plasticizers (DBP and DEP) were studied by network toxicology. Potential relevant targets were predicted through PharmMapper, SwissTargetPrediction, GeneCards, OMIM, DrugBank, and TTD databases. 143 relevant targets were identified and a network diagram was drawn. The study utilized Gene Ontology (GO) functional annotations, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) networks with cytoHubba plugin integration, ten relevant biological pathways (including pathways in cancer, lipid and atherosclerosis, prostate cancer, proteoglycan in cancer, Ras signaling pathway, endocrine resistance, MAPK signaling pathway, and so on), along with 10 central genes such as AKT1, GRB2, EGFR, HRAS, JAK2, PIK3CG, PIK3CD, PIK3R1, PTPN11, and SRC. Through molecular docking technology, this study showed that PIK3CG, PIK3CD, JAK2, HRAS, and PTPN11 had good binding affinity and interaction with the two plasticizers. This study not only revealed the molecular mechanism of plasticizer induced gastric cancer, but also highlighted the practical value of network toxicology in evaluating the toxicity of new environmental pollutants. The exposure of plasticizer may be an environmental trigger for the occurrence and development of gastric cancer, which emphasizes the potential environmental risk factors for the occurrence and development of plasticizer.