Work

Polyethylene nanoplastics promote tumor progression in canine mammary tumor U27 cells via the PPARγ–NF-κB axis

Year: 2026

Type: article

Abstract: Polyethylene nanoplastics (PE-NPs) are emerging environmental contaminants. The PPARγ-NF-κB signaling axis critically regulates inflammation and tumorigenesis, but its role in NP-induced cancer promotion is unknown. We investigated whether PE-NPs promote mammary tumor progression through this axis using canine mammary tumor (CMT-U27) cells as a translational model. Cells were exposed to 50-nm PE-NPs (0.25 mg/mL, 48 h). Transmission electron microscopy revealed intracellular PE-NP accumulation in autophagic lysosomes, mitochondrial enlargement, and apoptotic bodies. Transcriptomic analysis revealed dysregulation of pro-tumorigenic pathways including PPAR signaling. RT-qPCR and Western blotting confirmed PPARγ downregulation, NF-κB activation, and EMT marker changes: decreased E-cadherin and increased N-cadherin, Vimentin, and SNAIL (all P < 0.05). Functionally, PE-NPs significantly enhanced colony formation, cell migration, invasion, and tumorsphere formation (P < 0.01). Following PE-NP removal, MMP1, p65, N-cadherin, and SNAIL mRNA remained elevated at 72 h and 168 h (all P < 0.05), indicating persistent molecular alternations. In a mouse xenograft model, PE-NPs accelerated tumor growth (P < 0.001) and increased mitotic figures, Ki-67 expression, and intratumoral ROS levels (P < 0.001). Although there was no statistical difference, the PE group showed a trend of shorter survival. The PPARγ agonist rosiglitazone attenuated PE-NP-induced cell migration, invasion, and tumorsphere formation in vitro, as well as tumor growth in vivo, accompanied by reversal of EMT-associated marker changes and attenuation of PE-NP-induced p-p65 upregulation and IκBα downregulation (all P < 0.05). These findings reveal that PE-NPs promote mammary tumor progression via PPARγ-NF-κB axis dysregulation, representing an under-recognized environmental oncogenic risk, and identify PPARγ as a therapeutic target to mitigate NP-associated cancer risks.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2026.120948

Authors: Muyao Xu, Yuhan Wu, Zhaoyi Liu, Zixin Fang, Meng Li

Institution: Nanjing Agricultural University

Language: English

Topic: Microplastics and Plastic Pollution

Subfield: Pollution

Field: Environmental Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,650