Microplastics and nanoplastics are ubiquitous pollutants, widely spread in the living and natural environment. Although their potential impact on human health has been investigated, many doubts remain about their effects in carcinogenic processes. We investigated the potential effects and its molecular mechanisms of polystyrene nanoplastics (PS-NPs) on epithelial ovarian cancer (EOC) using the human EOC cell line HEY as an in vitro cell model and mice as a mammalian model. In vivo exposure to PS-NPs (100 nm; 10 mg/L) via drinking water significantly accelerated EOC tumor growth in mice. In in vitro tests the PS-NPs reduced the relative viability of EOC cells in a dose-dependent manner. Histological analysis showed increased mitotic counts in EOC tumor tissues of PS-NP exposed mice. PS-NP exposure significantly affected gene expression and disturbed many metabolic pathways in both cultured EOC cells and EOC tumor tissue in mice. Gene functional and pathway analysis indicated that immune-related responses and the tumor microenvironment pathway were significantly enriched, which may be attributed to disturbed expression of thrombomodulin (THBD) and its regulators. It may be concluded that PS-NP exposure caused a significant acceleration of EOC tumor growth in mice and a dose-dependent decrease in the relative viability of EOC cells by altering the tumor growth microenvironment. This offers new insights into the mechanisms underlying PS-NP effects on EOC.
Keywords: Epithelial ovarian cancer; Polystyrene nanoplastics; Thrombomodulin; Toxicogenomics; Tumor microenvironment.
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