Environmental nanoplastics exert dual effects: promoting tumor progression in cancer cells while inducing pyroptosis in normal esophageal epithelium.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor in the human digestive tract. The occurrence and development of esophageal cancer are closely related to environmental factors. As a new type of pollutant, microplastics have been intensively studied regarding their impact on health. The link between microplastics, an emerging environmental pollutant, and esophageal cancer remains uncertain, presenting a scientific question that requires investigation. This study utilized KYSE-30 and TE-1 esophageal squamous cell carcinoma cell lines in an in vitro model. Various biochemical experiments were conducted, such as MTT, flow cytometry, laser confocal microscopy, and Western-blot. Confocal microscopy observations showed that nanoplastics (NPs) were internalized into esophageal squamous cell carcinoma cells. Cell proliferation experiments indicated that NPs promoted the proliferation of esophageal cancer cell lines. Additional experiments demonstrated that NPs stimulation enhances glycolysis in esophageal cancer cells, leading to increased tumor cell proliferation. Mechanistic studies indicated that microplastics altered mitochondrial membrane potential, triggering mPTP opening and mt-DNA release into the cytoplasm, which activated the cGAS-STING-NF-κB signaling pathway. NF-κB enhances HIF-1α expression, leading to increased glycolysis and proliferation in esophageal cancer cells. In a normal esophageal epithelial cell model, we assessed the toxicological impact of nanoplastics, revealing that microplastics induced damage via NLRP3-mediated inflammation and pyroptosis. The study reveals that microplastics, as emerging pollutants, can enhance tumor cell proliferation and harm normal esophageal epithelium. These results suggest that NPs exhibit dual toxicological effects on tumor cells and normal esophageal epithelial cell models.