Page 177 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

SDIRSACR Oncology Insights

SESSION 14

INNOVATIVE MODELS AND APPROACHES IN CANCER RESEARCH

P91

Trophoblast-derived extracellular vesicles enhance cisplatin-induced apoptosis in ovarian cancer A2780
cells via Bax/Bcl-2 modulation

Jovana Vuković, Ninoslav Mitić, Mirjana Nacka Aleksić, Filip Janjić, Andrea Pirković

Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Belgrade, Serbia

Keywords: Ovarian cancer, extracellular vesicles, cisplatin, apoptosis, trophoblast

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 time-
dependent 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.

Acknowledgments and funding This research was supported by the Ministry of Science, Technological Development
and Innovation, Republic of Serbia, through a Grant Agreement with the University of Belgrade, Institute for the
Application of Nuclear Energy—INEP: 451-03-136/2025-03/200019.

162