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Updated: Feb 23, 2026
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Published on: November 2, 2014
Recovery from chronic PFAS exposure can reverse chemotherapy resistance and mitochondrial alterations in ovarian
Brittany P Rickard1, Lauren A Sapienza-Lundie2, Vesna A Chappell3
1Department of Biological Sciences, North Carolina State University, Raleigh, NC 27606, USA; Curriculum in Toxicology & Environmental Medicine, University of North Carolina School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lampe Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA, and North Carolina State University, Raleigh, NC 27606, USA.
Abstract:
Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants of global concern that have been associated with a variety of adverse health outcomes, including diminished chemotherapy response. Previous studies in moderately chemosensitive ovarian cancer cells (OVCAR-3) have shown that the induction of chemoresistance from PFAS exposure is duration-dependent, with longer, more human-relevant exposure durations leading to worse outcomes. Mitochondrial content was also altered following chronic PFAS exposure, suggesting mitochondria as contributors to PFAS-induced chemoresistance. Here, chemotherapy response following chronic PFAS exposure in a chemoresistant human ovarian cancer cell line, OVCAR-8, was evaluated. Compared to OVCAR-3 cells, chemotherapy response was unaffected by chronic PFAS exposure in OVCAR-8 cells. As individuals gain awareness of sources of PFAS exposure, and associated harmful effects, actions can be taken to limit exposure using water filtration systems and/or safer alternatives to PFAS-containing consumer goods. Thus, we also explored the ability of PFAS-sensitive OVCAR-3 cells to recover from chronic exposure. Following 6 passages of chronic PFAS exposure, cells were "outgrown" in the absence of PFAS for 7 additional passages and proliferation, chemotherapy response, and mitochondria-related alterations were assessed. Compared to chronically-exposed cells, outgrown cells displayed heightened sensitivity to chemotherapy along with decreased superoxide production and mitochondrial content. Proliferation remained significantly elevated compared to controls, suggesting that not all PFAS-induced effects are abrogated by a recovery period. Together, these findings suggest that ovarian cancer cells differ in their PFAS sensitivities and that mitochondria-related alterations resulting from chronic PFAS exposure can be reversed following a "recovery period", potentially resensitizing cancer cells to chemotherapy.
