Chronic Exposure to Polystyrene Nanoplastics Promotes Lung Cancer Progression via Activating Gluconeogenesis and Inhibiting Glycolysis

作者：Qian Li, Wenwen Meng, Lang Wen, Chengting Xie, F Wang, Ziyi Guo, Zhaoxiang Yan, Yating Deng, Keying Chen, Y H Li, Yixian Wen, Tingli Han, Fei Han · 发表于：Environment & Health · 年份：2026 · DOI：10.1021/envhealth.5c00487 · 被引用次数：1 · 研究领域：Microplastics and Plastic Pollution、biodegradable polymer synthesis and properties、Immune cells in cancer

High Resolution Image Download MS PowerPoint Slide Nanoplastics (NPs) are emerging as environmental pollutants, yet their long-term impact on lung cancer progression remains largely unexplored. This study explored the influence of extended exposure to polystyrene nanoplastics (PS-NPs) on the growth and movement of A549 lung cancer cells, with particular emphasis on the molecular mechanisms involved in metabolic reprogramming. We demonstrated that prolonged exposure to PS-NPs markedly increased the ability of lung cancer cells to proliferate and migrate. Using an integrated approach combining transcriptomic profiling and C 13 -labeled glucose flux analysis, we observed that chronic PS-NPs exposure induced metabolic reprogramming characterized by the activation of gluconeogenesis and suppression of glycolysis. Mechanistically, PS-NPs upregulated the gluconeogenic enzyme mitochondrial phosphoenolpyruvate carboxykinase (PCK2) and downregulated enolase-1 (ENO1), a glycolytic enzyme. Notably, knockdown of PCK2 attenuated PS-NPs-induced cell proliferation and migration, underscoring its functional role. We further identified that stress-responsive activating transcription factor-3 (ATF3) serves as a crucial mediator of PCK2 and ENO1 expression. Chromatin immunoprecipitation followed by PCR (ChIP-PCR) confirmed enhanced binding of ATF3 to the promoter regions of PCK2 and ENO1 upon PS-NPs exposure. Silencing ATF3 abolished PS-NPs-induced changes in PCK2 and ENO1 expression and blocked...