Abstract

Background Acetyl tributyl citrate (ATBC), a widely used plasticizer, has raised health concerns due to its potential environmental persistence and human exposure, but its toxicological effects on sarcoma remain unclear. Methods We employed an integrated approach combining network toxicology, molecular docking, survival analysis, and experimental validation to systematically investigate ATBC’s impact on sarcoma. Results Multi-database screening identified 102 overlapping targets. Protein–protein interaction analysis revealed six hub genes: TLR4, ESR1, PPARG, SIRT1, NFKB1, and PTGS2. Functional enrichment analysis indicated significant involvement in cancer-related pathways, including PI3K–Akt, HIF‑1, and AGE–RAGE signaling. Molecular docking predicted potential interactions between ATBC and these targets, with binding energies ranging from -1.15 to -2.99 kcal/mol. Survival analysis associated high PPARG expression with poor prognosis, while high TLR4 and ESR1 expression correlated with better survival. In vitro experiments showed ATBC promoted proliferation and migration of sarcoma cells. qPCR results confirmed ATBC downregulated TLR4 and ESR1 and upregulated PPARG, aligning with clinical prognostic trends. Conclusions These findings suggest ATBC may exert tumor-promoting effects by modulating core targets and pathways, highlighting its potential role in sarcoma progression and the importance of environmental health risk assessment.