Polyethylene nanoplastics promote tumor progression in canine mammary tumor U27 cells via the PPARγ–NF-κB axis
- 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China
- 2Correspondence to: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Nanjing Agricultural University, No. 1 Weigang, Nanjing, Jiangsu 210095, China.
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.
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BibTeX
@article{xu2026polyethylene,
title = {{Polyethylene nanoplastics promote tumor progression in canine mammary tumor U27 cells via the PPARγ–NF-κB axis}},
author = {Muyao Xu and Yuhan Wu and Zhaoyi Liu and Zixin Fang and Meng Li},
journal = {Ecotoxicology and Environmental Safety},
year = {2026},
month = oct,
doi = {10.1016/j.ecoenv.2026.120948},
url = {https://doi.org/10.1016/j.ecoenv.2026.120948},
note = {CC BY},
}
RIS
TY - JOUR
TI - Polyethylene nanoplastics promote tumor progression in canine mammary tumor U27 cells via the PPARγ–NF-κB axis
AU - Muyao Xu
AU - Yuhan Wu
AU - Zhaoyi Liu
AU - Zixin Fang
AU - Meng Li
PY - 2026
DA - 2026/10/24
JO - Ecotoxicology and Environmental Safety
DO - 10.1016/j.ecoenv.2026.120948
UR - https://doi.org/10.1016/j.ecoenv.2026.120948
AB - 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.
SN - 0147-6513
SN - 1090-2414
ER -