Perfluorooctanoic acid and perfluorooctanesulfonic acid induce resistance to chemotherapy in colorectal cancer.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) are non-volatile environmental pollutants that are ubiquitous in nature. Colorectal cancer (CRC) is one of the most common malignant tumors, with high incidence and mortality rates worldwide. As one of the primary treatment modalities for CRC, chemotherapy often encounters drug resistance as its greatest obstacle to effective treatment. Exposure to PFAS has been shown to be associated with the progression of multiple tumors and the impact on treatment responses. However, their association with the efficacy of chemotherapy treatment for CRC remains unclear. This study aims to systematically investigate the effects of PFOA and PFOS on chemotherapy resistance in CRC and their underlying molecular mechanisms through in vitro and in vivo experiments. The results indicated that PFOA and PFOS significantly increased the resistance of HCT116 and SW620 cells to Oxaliplatin (OXA), 5-Fluorouracil (5-FU), and Irinotecan (CPT-11). Further studies revealed that PFOA and PFOS reverse the cell cycle arrest effect of chemotherapeutic drugs on CRC cells by regulating the expression of Cyclin A2 and CDK2. Exposure to PFAS may potentially elevate the risk of chemotherapy resistance in CRC, a finding that has significant implications for clinical treatment and chemical risk assessment.