Low-dose polystyrene microplastics exposure promotes human prostate cancer cell proliferation via GPX4‑mediated ferroptosis

Microplastics are increasingly recognized as potential threats to human health. In our previous study, polystyrene microplastics (PS-MPs) were detected in both para-tumor and tumor tissues of human prostate samples, with significantly higher abundance observed in tumor tissues compared to their paired para-tumor counterparts. However, whether and how PS-MPs contribute to the progression of prostate cancer remains poorly understood. This study aims to investigate the effects and underlying mechanisms of PS-MPs exposure on the proliferation of human prostate cancer cells. To this end, we exposed both the human prostate cancer cell line LNCaP and primary cultured human prostate cancer cells to varying doses of 1-μm-diameter PS-MPs. Our results showed that low-dose (0.1 μg/mL) PS-MPs exposure for 48 significantly promoted the proliferation of LNCaP cells. Additionally, PS-MPs exposure altered the expression of certain inflammatory factors and induced oxidative stress in LNCaP cells. We also observed upregulation of GPX4 and ACSL4 in LNCaP cells and primary prostate cancer cells following PS-MPs exposure. Notably, GPX4 knockdown reversed the effects of PS-MPs on reactive oxygen species (ROS) levels, lipid peroxidation, and glutathione content, likely by promoting ferroptosis. Taken together, our findings highlight a critical role for ferroptosis in PS-MPs-induced proliferation of human prostate cancer cells under low-dose exposure.