Polystyrene Nanoplastics at an Environmentally Relevant Concentration Promote Ovarian Cancer Progression via CDK4/6-Dependent Signaling

Abstract

Nanoplastics (NPs) are emerging global contaminants, which are known to harm respiratory, digestive, neural, and cardiovascular systems; their tumorigenic risks at environmentally relevant levels remain unclear. Here, we sought to clarify the potential promoting effects of PS-NPs on ovarian cancer. Our results first showed that ovarian cancer cells could internalize 50 nm PS-NPs, with significant internalization observed at concentrations starting from 20 μg/mL, which aligns with environmental exposure levels. RNA-seq and subsequent experiments indicated that treatment with 20 μg/mL PS-NPs significantly promoted ovarian cancer cell proliferation, and this phenotype was closely associated with CDK4/6-dependent cell cycle regulation. The CDK4/6 inhibitor Palbociclib effectively reverses the cell proliferation induced by PS-NPs. An oral exposure model in mice found tissue deposition of PS-NPs in the ovaries, kidneys, heart, and lungs. In vivo models further confirmed that mice exposed to PS-NPs had larger subcutaneous tumor weights and volumes compared to the control group, while Palbociclib could successfully block these effects. In conclusion, our research revealed that low-dose PS-NPs could stimulate ovarian tumor progression both in vivo and in vitro in a CDK4/6-dependent manner. Taken together, our study provides potential evidence for risk management of exposure to nanoplastics related to cancer development.