PFOS and Its Commercial Alternative, 6:2 Cl-PFESA, Induce Multidrug Resistance in Pancreatic Cancer

Area of Science:

• Environmental Health
• Oncology
• Toxicology

Background:

• Per- and polyfluoroalkyl substances (PFAS), including perfluorooctanesulfonate (PFOS) and its alternative 6:2 Cl-PFESA, are linked to health concerns.
• The impact of PFAS on multidrug resistance (MDR) in pancreatic cancer (PC) chemotherapy is not well understood.

Purpose of the Study:

• To investigate the correlation between PFOS/6:2 Cl-PFESA exposure and MDR in pancreatic cancer.
• To elucidate the molecular mechanisms underlying PFAS-induced MDR in PC.

Main Methods:

• Utilized drug-sensitivity assays (IC50), in vitro/in vivo PC models, and paclitaxel (PTX) as a representative chemotherapeutic.
• Employed transcriptomic/proteomic sequencing and clinical prognostic analysis to identify MDR-related genes.
• Assessed the activation of the PI3K-ABCB1 pathway.

Main Results:

• PFOS/6:2 Cl-PFESA exposure increased drug IC50 values in PC cell lines.
• 6:2 Cl-PFESA exhibited a stronger pro-MDR effect than PFOS in vitro.
• PFAS exposure significantly reduced PTX efficacy in vivo and activated the PI3K-ABCB1 pathway, with 6:2 Cl-PFESA showing greater potency.

Conclusions:

• PFAS exposure may increase pancreatic cancer MDR and disease progression risk.
• The alternative PFAS, 6:2 Cl-PFESA, demonstrates significant MDR-promoting effects, necessitating comprehensive risk assessment.
• Findings highlight the need to evaluate the carcinogenic potential and MDR-inducing properties of PFAS alternatives.