Work

Dibutyl phthalate promotes COAD cells growth and migration via the TIMP1/PI3K/AKT signaling axis

Year: 2025

Type: article

Abstract: Dibutyl phthalate (DBP), a widely used plasticizer due to its excellent plasticizing properties, is extensively applied in food packaging and medical devices. Accumulating evidence indicates that DBP exposure is closely linked to the proliferation of malignant tumors. However, its role in the progression of colon adenocarcinoma (COAD) remains to be thoroughly investigated. In this study, Cox regression and LASSO regression analyses were utilized to identify key genes involved in DBP-mediated COAD development. A multi-gene prognostic risk prediction model was developed and validated. Additionally, the effects of DBP exposure on the proliferation, colony formation, and migration of Caco-2 and HT-29 cells were evaluated, and the underlying molecular mechanisms were explored. Results showed that DBP significantly enhanced the proliferation, colony-forming capacity, and migration of Caco-2 and HT-29 cells at concentrations as low as 1 nM, with the maximum effect observed at 10 μM. Bioinformatics analyses constructed a prognostic model containing 10 genes, among which TIMP-1 was significantly upregulated in high-risk populations and positively correlated with the DBP concentration gradient. Functional validation demonstrated that TIMP-1 knockdown effectively inhibited DBP-induced cell proliferation and significantly reduced the phosphorylation levels of the PI3K/AKT signaling pathway, suggesting that TIMP-1 may mediate the pro-carcinogenic effects of DBP by regulating the PI3K/AKT axis. This study highlights the critical impact of DBP on colon cancer cell progression and provides a theoretical foundation for evaluating the genotoxicity of DBP.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2025.118931