Microplastics exposure promotes the proliferation of skin cancer cells but inhibits the growth of normal skin cells by regulating the inflammatory process.

Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignant tumors of the skin, occurring primarily in the elderly population. CSCC is the second most common nonmelanoma skin malignancy in humans. The development of cutaneous squamous cell carcinoma is closely linked to environmental factors. Microplastics, as a new pollutant, are currently being intensively studied for their potential health effects. However, the effect of microplastics on skin cancer is not yet known and is an important scientific question that needs to be addressed. To this end, in the current study, two skin squamous cell carcinoma cell lines (SCL-1 and A431) were utilized to investigate the effects of microplastics on skin cancer, and cell behavior experiments showed that microplastics were internalized into the skin squamous cell carcinoma cell line in a time- and dose-dependent manner. Further experiments showed that microplastics promoted the proliferation of skin cancer cells by MTT, flow cytometry, laser confocal microscopy, Western blotting and other experimental techniques. Mechanistic studies showed that microplastics could lead to increased mitochondrial ROS in skin cancer cells, which in turn caused a change in mitochondrial membrane potential, thus opening mPTP, which in turn caused the release of mt-DNA from mitochondria into the cytoplasm, thus activating NLRP3 and ultimately causing skin cancer cell proliferation. We further evaluated the effect of microplastics on HaCaT cells in a normal skin cell model and showed that microplastics caused damage to normal skin cells through NLRP3-mediated inflammation and scorch death. The current study suggests that microplastics, as a new contaminant, may promote tumor cell proliferation while causing damage to normal skin.