Polyvinyl chloride microplastics exposure accelerates endometrial cancer progression via regulating AHR/CYP1A1 signaling pathway.

Endometrial cancer (EC) is one of the most prevalent gynaecological cancers among women. Despite the advent of advanced therapeutic approaches, the mortality rate of EC has not declined but rather shows an increasing trend, which is closely associated with its rising incidence. No viable strategies have been established to curb the rising incidence of EC. Polyvinyl hloride microplastics (PVC-MPs) represent ubiquitous environmental contaminants. Increasing evidences demonstrate the carcinogenic potential of PVC-MPs exposure. However, PVC-MPs specific role and mechanisms in EC remain unelucidated. This study provides the first comprehensive evidence that PVC-MPs exacerbate EC progression by activating the AHR/CYP1A1 pathways, driving proliferation, migration, invasion. The tumor-promoting effects of PVC-MPs were further validated in primary human endometrial cancer cells and mouse models (including both cell line-derived xenograft and patient-derived xenograft), substantially strengthening the robustness and translational relevance of our study. Collectively, these findings establish PVC-MPs as an environmental risk factor for EC and identify AHR/CYP1A1 signaling pathway as potential therapeutic targets to mitigate the adverse effects of microplastic exposure, developing preventive interventions in exposed populations against EC (Graphic abstract).