Microplastics promote chemoresistance by mediating lipid metabolism and suppressing pyroptosis in colorectal cancer

Microplastics are ubiquitous environmental contaminants worldwide. Although studies have shown their potential to harm human health, the relationship between microplastics and tumors remains unclear. The intestine is the primary site for microplastics absorption, thus the impact of microplastics on colorectal cancer merits further investigation. Our results indicate that the endocytosis protein clathrin, highly expressed in cancer cells, plays a crucial role in the massive ingestion of microplastics. Further research reveals that microplastics ingestion enhances lipid absorption in colorectal cancer cells by activating the NF-κB signaling pathway. Accumulation of lipids, in turn, suppresses pyroptosis by inhibiting NLRP3/Caspase-1/GSDMD axis, thereby promoting cellular drug resistance. Moreover, microplastics accelerate colorectal cancer development in mice and enhance tumor resistance to oxaliplatin. In summary, microplastics regulate lipid metabolism and pyroptosis in colorectal cancer, emerging as a novel contributor to chemotherapy resistance in colorectal cancer against the backdrop of escalating microplastics pollution.