Polystyrene nanoplastics and lung cancer: Insights from network toxicology and mechanistic in vitro studies

The correlation between exposure to polystyrene nanoplastics (PNs), an emerging environmental pollutant, and cancer processes has attracted heightened attention. However, the potential effects of PNs exposure on the processes of lung cancer have been yet inadequately comprehended. Our current study investigated the effects and mechanisms of PNs on lung cancer based on network toxicity analysis and in vitro tests. The integrated network toxicology analysis identified 189 possible targets of PNs-induced lung cancer, primarily associated with oxidative stress, apoptosis, inflammation, mitochondrial outer membranes, and cancer pathways. The 10 primary targets extracted from protein-protein interaction (PPI) analysis exhibited strong binding affinities with PNs (-8.7 to -5.2 kcal/mol) via molecular docking. The A549 human lung adenocarcinoma cells exhibited cytotoxicity after exposure to PNs via cell morphology analysis, MTT assay, and LDH assay. Additionally, treatment with PNs in A549 cells induced cell death, diminished mitochondrial membrane potential, elevated ROS and MDA levels, activated the cellular antioxidant defense system by enhancing SOD and GST activity, excited the release of IL-6, IL-1β, and TNF-α, and captured the cell cycle in the G0/G1 phase. This study suggests that PNs not only elicit cytotoxicity but also contribute to lung cancer progression, providing critical insights into the potential carcinogenic hazards linked to PNs and underscoring the pressing necessity for regulatory oversight of PNs exposure to protect public health and environmental risks associated with nanoplastics pollution.