Chronic PFAS exposure induces chemotherapy resistance by promoting mitochondria-related alterations in ovarian cancer cells
Year: 2025
Type: article
Abstract: Resistance to chemotherapy is a major barrier to the effective treatment of ovarian cancer; however, the role of environmental exposures in the onset of chemoresistance remains elusive. Our previous work in ovarian cancer cells suggests that short-term perfluoroalkyl substances (PFAS) exposures induce chemoresistance, potentially by influencing mitochondrial parameters, but little is known about the effects of longer-term exposures, which are more human-relevant. Since mitochondria play critical roles in determining ovarian cancer chemotherapy response, it is also important to understand the role of environmental exposures in modulating mitochondrial function. This study explored how varying durations of PFAS exposure (2-35 days) affect mitochondrial parameters known to drive chemoresistance in human ovarian cancer cell lines. An ovarian cancer cell line (OVCAR-3) that was chronically exposed to PFAS (26-35 days) was generated. Compared to short-term PFAS exposure, chronic PFAS exposures significantly increased resistance to both carboplatin and doxorubicin. Chemotherapy resistance was accompanied by increased mitochondrial superoxide production, alterations in bioenergetics, and elevated mitochondrial content. These findings suggest that PFAS exposure induces chemotherapy resistance in ovarian cancer cells in a duration-dependent manner, worsened by human-relevant chronic exposures, and that mechanisms driving these effects are influenced by the modulation of mitochondrial parameters. Future studies should focus on targeting mechanisms underlying PFAS-induced chemotherapy resistance to improve survival outcomes.
Source: Environmental Research
Institutions: University of North Carolina at Chapel Hill, North Carolina State University, Lampe Joint Department of Biomedical Engineering, National Institutes of Health, National Institute of Environmental Health Sciences, Environmental Protection Agency, UNC Lineberger Comprehensive Cancer Center
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,880
Funders: U.S. Environmental Protection Agency, University of North Carolina, North Carolina State University, Environmental Protection Agency, U.S. Food and Drug Administration, Office of Research, Drexel University, University of North Carolina at Chapel Hill, National Cancer Institute, National Institute of Environmental Health Sciences, Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill
Awards: Targeting Fluid Stress-induced Chemoresistance in a 3D Carcinomatosis Perfusion Model Using Mechanism-based Photo-immunoconjugate Nanoparticles, UNC Center for Environmental Health and Susceptibility, Pre- and Postdoctoral Training in Toxicology, Center for Human Health and the Environment (CHHE)
OpenAlex ID: W4411504386