By Pooja Toshniwal PahariaReviewed by Lauren HardakerNov 19 2025New research reveals that tiny plastic particles, commonly found in food, water, and air, can accelerate ovarian tumor growth. Meanwhile, scientists have also identified a potential drug that may block their cancer-promoting impact.
Image credit: MAXSHOT.PL/Shutterstock.com
A recent study published in Environment & Health shows that polystyrene nanoplastics (PS-NPs) at environmentally relevant levels can accelerate ovarian cancer progression. Fifty-nanometer PS-NPs accumulated in mouse ovaries and boosted tumor growth in both cells and animal models by activating cyclin-dependent kinase 4 and 6 (CDK4/6)-dependent cell-cycle pathways.
Transcriptomic analyses confirmed broad cell-cycle disruption, while Palbociclib largely reversed these effects in vitro and partially reversed PS-NP–induced tumor-marker changes in vivo. These findings provide early mechanistic evidence that repeated NP exposure may elevate risks for ovarian cancer.
Rising Exposure to Nanoplastics
Nanoplastics (NPs) have become environmental contaminants, yet their effects on female reproductive health remain poorly understood. Formed from the breakdown of larger plastics, these particles are widely present in air, water, and food, with human exposure reaching levels of tens of micrograms per mL.
Their small size enables them to cross cell membranes, circulate systemically, and carry adsorbed pollutants, contributing to multi-organ toxicity. PS-NPs can accumulate in organs, inducing inflammation, apoptosis, and tissue damage. While microplastics have accumulated in ovarian tissues, the impact of NPs on ovarian cancer progression is still unclear.
Examining Cancer Responses to Nanoplastics
In the present study, researchers investigated whether environmentally representative PS-NP concentrations promote ovarian cancer growth and explored the underlying mechanisms using an integrated in vitro and in vivo approach. For the analysis, they characterized PS-NPs using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, particle diameter, and zeta potential measurements. They also cultured A2780 and SKOV3 human ovarian cancer cell lines under standard conditions.
To assess cytoskeletal changes, researchers exposed cells to fluorescently labeled PS-NPs (0 to 80 µg/mL) for 24 hours and stained them with F-actin staining for confocal microscopy. Cellular pretreatment with clathrin- and caveolin-mediated endocytosis inhibitor molecules before PS-NP exposure enabled the identification of uptake mechanisms.
Cell counting kit-8 (CCK-8) viability assays, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays, and clonogenic assay evaluated the impact of PS-NPs on cell proliferation. Ribonucleic acid (RNA) sequencing on cells treated with PS-NPs (20 µg/mL) characterized transcriptomic changes.
Gene Ontology (GO) enrichment analysis determined enrichment of cell cycle–related pathways, followed by quantitative polymerase chain reaction (PCR), Western blotting, and immunofluorescence for further validation. In addition, the team assessed the effects of Palbociclib, a CDK4/6 inhibitor, based on its ability to reduce p-Rb levels at one µM rather than solely on half-maximal inhibitory concentration (IC₅₀) values.
Further, researchers established a BALB/c mouse subcutaneous xenograft model for in vivo assessment. The mice were randomized into four groups: control, PS-NPs, Palbociclib, and PS-NPs + Palbociclib (n = 6 per group). These animals received PS-NPs via daily gavage (25 mg/kg/day) and Palbociclib (40 mg/kg/day) for four weeks, with continuous tumor growth monitoring during the treatment period. After euthanasia, the team imaged major organs (such as ovaries, heart, kidneys, and lungs) by immunofluorescence to track PS-NP distribution and performed immunohistochemistry specifically on tumor tissues for further evaluation.
How Nanoplastics Affect Cells
The team found that ovarian cancer cells could effectively internalize 50 nm PS-NPs, with prominent uptake at 20 μg/mL, an exposure level consistent with environmental estimates. TEM, size distribution analysis, and FTIR confirmed the nanoscale diameter, uniform spherical morphology, and chemical identity of the PS-NPs, while a Zeta potential of –31.4 mV indicated good colloidal stability.
Fluorescence and electron microscopy showed a dose- and time-dependent internalization of polystyrene NPs in A2780 and SKOV3 cells, with marked uptake after 24 hours. Endocytosis-inhibition assays confirmed that PS-NPs entered cells predominantly through a clathrin-mediated pathway. Functionally, PS-NPs did not impair cell viability but instead promoted proliferation in a concentration-dependent manner commencing at 20 μg/mL, as demonstrated by EdU incorporation and colony formation assays.
Transcriptomic profiling after exposure to 20 μg/mL revealed a strong enrichment of cell-cycle pathways, with CDK4, CDK6, Cyclin D1, and p-Rb being markedly upregulated at both the messenger RNA (mRNA) and protein levels. Immunofluorescence confirmed increased p-Rb, indicating accelerated cell-cycle progression. Survival analysis using the AOCS ovarian cancer dataset further linked higher CDK4/6 expression to poorer clinical outcomes in ovarian cancer patients.
Palbociclib (1.0 μmol/L) effectively suppressed PS-NP–induced proliferation, evidenced by reduced EdU incorporation, diminished colony formation, and downregulation of CDK4, cyclin D1, and p-Rb. Ki67 staining further confirmed suppression of PS-NP–driven cell-cycle activation.
In vivo, fluorescent PS-NPs accumulated in the ovaries, heart, kidneys, and lungs after oral exposure. PS–NP–treated mice developed significantly larger tumors, whereas co-treatment with Palbociclib markedly reduced tumor weight and volume. Tumor immunohistochemistry mirrored in vitro findings, with increased Ki67, CDK4/6, Cyclin D1, and p-Rb in PS-NP–exposed mice, and partial reversal following Palbociclib.
Implications for Female Health
This study demonstrates that environmentally relevant doses of PS-NPs can accelerate ovarian cancer progression by activating CDK4/6-mediated cell cycle pathways. Notably, the CDK4/6 inhibitor Palbociclib attenuated these effects in both cell and animal models, suggesting a promising strategy to counteract NP-induced tumor growth.
These findings heighten concerns about the health risks associated with widespread NP exposure and highlight the need for stronger environmental controls and public health measures.
Future work should explore long-term, low-dose exposure effects, impacts on normal ovarian tissue, limitations such as the use of a subcutaneous xenograft model and only one nanoplastic type, and responses to different NP types to improve risk assessment and prevention.
Download your PDF copy now!
Journal Reference
Xiaoyu Yuan et al. (2025). Polystyrene Nanoplastics at an Environmentally Relevant Concentration Promote Ovarian Cancer Progression via CDK4/6-Dependent Signaling. Environment & Health, DOI: 10.1021/envhealth.5c00329. https://pubs.acs.org/doi/10.1021/envhealth.5c00329
Ferroptosis Suppression Identified as a Key Driver of Lung Cancer Growth