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Select Per- and Polyfluoroalkyl Substances (PFAS) Induce Resistance to Carboplatin in Ovarian Cancer Cell Lines

Brittany P. Rickard, Xianming Tan, Suzanne E. Fenton, and Imran Rizvi
International Journal of Molecular Sciences (2022), 23(9), 5176; DOI: https://doi.org/10.3390/ijms23095176

DOI: https://doi.org/10.22427/NTP-DATA-025-00001-0002-000-0


Publication


Abstract

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants associated with adverse reproductive outcomes including reproductive cancers in women. PFAS can alter normal ovarian function, but the effects of PFAS on ovarian cancer progression and therapy response remains understudied. Ovarian cancer is the most lethal gynecologic malignancy, and a major barrier to effective treatment is resistance to platinum-based chemotherapy. Platinum resistance may arise from exposure to external stimuli such as environmental contaminants. This study evaluated PFAS and PFAS mixture exposures to two human ovarian cancer cell lines to evaluate the ability of PFAS exposure to affect survival fraction following treatment with carboplatin. This is the first study to demonstrate that, at sub-cytotoxic concentrations, select PFAS and PFAS mixtures increased survival fraction in ovarian cancer cells following carboplatin treatment, indicative of platinum resistance. A concomitant increase in mitochondrial membrane potential, measured by the JC-1 fluorescent probe, was observed in PFAS-exposed and PFAS + carboplatin-treated cells, suggesting a potential role for altered mitochondrial function that requires further investigation.

Results


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Figures


Figure 1. Concentration-dependent effect of methanol on survival fraction in two ovarian cancer cell lines

Figure 2. PFAS are sub-cytotoxic in ovarian cancer cell lines at selected nanomolar and micromolar concentrations

Figure 3. PFAS mixtures increase survival fraction in ovarian cancer cells

Figure 4. Dose–response to carboplatin in OVCAR-3 and Caov-3 cells

Figure 5. PFAS increase survival fraction in ovarian cancer cells treated with carboplatin

Figure 6. PFAS mixtures increase survival fraction following treatment with carboplatin in ovarian cancer cells

Figure 7. Exposure to certain PFAS led to an increase in ΔΨm while carboplatin treatment decreased ΔΨm

Figure 8. ΔΨm increases in OVCAR-3 and Caov-3 cells exposed to PFAS or PFAS mixtures then treated with carboplatin

Supplemental Materials


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