Digitalni repozitorijum
Univerziteta u Beogradu
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Trophoblast-derived extracellular vesicles enhance cisplatin-induced apoptosis in ovarian cancer A2780 cells via Bax/Bcl-2 modulation
Nacka-Aleksić, Mirjana
Janjić, Filip
Pirković, Andrea
Vuković, Jovana
Mitić, Ninoslav
Background: Ovarian cancer is the leading cause of death among gynecological malignancies, associated with frequent chemoresistance. Extracellular vesicles (EVs) from the placenta have recently shown therapeutic potential by altering the ovarian tumor cell phenotype, though the precise mechanisms remain unclear. The aim of this study was to investigate whether EVs from trophoblast cells (TC-EVs) could affect the viability of ovarian cancer A2780 cells and improve their sensitivity to cisplatin. Material and methods: TC-EVs were isolated from the conditioned media of the trophoblast cell line HTR-8/SVneo using differential ultracentrifugation. Analysis of the concentration and size distribution of total, as well as CD9-and CD81-positive TC-EVs, was performed using a nanoparticle tracking analyzer. Ovarian cancer cells A2780 were preconditioned with TC-EVs (50 μg/mL protein) for 24 or 48 hours, followed by treatment with 15 μM cisplatin. Cell viability was assessed by MTT assay, and changes in the expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 mRNA were quantified using qPCR. Results: At the 24h treatment, cisplatin treatment markedly reduced the viability of A2780 cells, and there was no difference between TC-EVs preconditioned cells and cells exposed to cisplatin alone. However, at the 48-hour treatment, preconditioning with TC-EVs produced a statistically significant additional decrease in cell viability compared to cisplatin alone, indicating a potential sensitizing effect of TC-EVs. This was accompanied by increased Bax and decreased Bcl-2 expression, resulting in a higher Bax/Bcl-2 ratio in TC-EVs preconditioned cells, indicating a pro-apoptotic shift. Conclusions: Trophoblast-derived EVs display in vitro cisplatin-sensitizing effects in ovarian cancer cells in a timedependent manner, likely by modulating pro-apoptotic pathways. This suggests that TC-EVs might play a role in improving the effectiveness of platinum-based ovarian cancer chemotherapy.
engleski
2025
Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 4.0 - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 4.0 International License.
http://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
Ovarian cancer, extracellular vesicles, cisplatin, apoptosis, trophoblast