20.500.12556/RUL-184069 Citotoksični učinek spojine BOLD-100 v kombinaciji z elektroporacijo na celično linijo raka trebušne slinavke PANC-1 Cytotoxic effect of BOLD-100 in combination with electroporation in the PANC-1 pancreatic cancer cell line Rak trebušne slinavke zaznamuje izrazito slaba prognoza, obstoječe možnosti zdravljenja pa pogosto ne dosegajo zadovoljive učinkovitosti, zato ostaja potreba po razvoju novih, bolj učinkovitih pristopov zdravljenja velika. Elektrokemoterapija (EKT) predstavlja obetavno tehniko lokalnega ablativnega zdravljenja, ki temelji na uporabi reverzibilne elektroporacije za začasno povečanje prepustnosti celičnih membran, s čimer omogoča učinkovitejši vnos citostatikov v celice in posledično potencira njihov citotoksični učinek. V uporabi z EKT še ni bil testiran BOLD-100, citostatik na osnovi rutenija, ki v kliničnih študijah kaže visoko protitumorsko učinkovitost. V magistrski nalogi smo zato želeli ovrednotiti učinek BOLD-100 v kombinaciji z EKT v in vitro pogojih na celični liniji raka trebušne slinavke PANC1. Učinek BOLD-100 smo primerjali s citostatikom cisplatinom (CDDP), ki se rutinsko uporablja v klinični EKT. Celice smo izpostavili različnim koncentracijam BOLD-100 in cisplatina z ali brez izvedbe elektroporacije. Viabilnost celic smo določali s testom PrestoBlue, 1, 3 in 7 dni po tretmaju. Na podlagi dobljenih podatkov smo izračunali IC30, IC50 in IC70 ter izvedli statistično analizo z dvosmerno analizo variance (ANOVA). Pridobljeni rezultati kažejo na močno potenciranje učinka BOLD-100. Citotoksični učinek je hiter, upad preživetja smo zaznali že prvi dan po izvedbi EKT. S časom se učinek dodatno stopnjuje, najnižje vrednosti IC50 smo dosegli sedmi dan po izpostavitvi. Brez EKT spojina BOLD-100 ni bistveno vplivala na preživetje celic. EKT je potencirala tudi učinek CDDP, vendar so bili citotoksični učinki počasnejši in manj izraziti v primerjavi z BOLD-100. Rezultati nakazujejo, da bi BOLD-100 v EKT lahko predstavljal učinkovito alternativo obstoječim terapijam, zlasti pri tumorjih z razvito rezistenco na cisplatin. Pancreatic cancer is characterized by a particularly poor prognosis. Existing treatment options often fail to achieve adequate efficacy, so there remains a significant need to develop new, more effective treatment approaches. Electrochemotherapy (ECT) represents a promising therapeutic method based on the use of reversible electroporation to temporarily increase the permeability of cell membranes, thereby enabling more effective delivery of cytostatic drugs into cells and consequently potentiating their cytotoxic effect. BOLD-100, a ruthenium-based cytostatic agent that demonstrates high antitumor efficacy in clinical studies, has not yet been tested in combination with ECT. In this master’s thesis, we therefore sought to evaluate the effect of BOLD-100 in combination with ECT under in vitro conditions on the PANC1 pancreatic cancer cell line. We compared the effect of BOLD-100 with the cytostatic agent cisplatin (CDDP), which is routinely used in clinical ECT. We exposed the cells to various concentrations of BOLD-100 and cisplatin with or without electroporation. Cell viability was determined using the PrestoBlue assay 1, 3, and 7 days after treatment. Based on the obtained data, we calculated IC30, IC50, and IC70 and performed a statistical analysis using a two-factor ANOVA test. The results indicate a strong potentiation of the effect of BOLD-100. The cytotoxic effect is rapid; a decrease in cell viability was observed as early as the first day after ECT. The effect further intensified over time, with the lowest IC50 values reached on the seventh day after exposure. Without ECT, the BOLD-100 compound did not significantly affect cell survival. ECT also potentiated the effect of CDDP, but the cytotoxic effects were slower and less pronounced compared to BOLD-100. The results suggest that BOLD-100 ECT could represent an effective alternative to existing therapies, particularly for tumors with developed resistance to cisplatin. BOLD-100 elektrokemoterapija elektorporacija PANC-1 cisplatin BOLD-100 electrochemotherapy electroporation PANC-1 cisplatin true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2026-06-25 08:16:01 2026-06-25 08:16:12 2026-06-30 10:44:16 0000-00-00 00:00:00 2026 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 280261 283058691 57921.pdf 57921.pdf 1 9166D912D24E1E004628E27378C7B6DC 95390b6413c6c6d5d6a0a9b96b1058093d02af3ad3c71af7b4c10a990287bae5 470db011-705d-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=236528 Biotehniška fakulteta 0 0 0