The prognosis of pancreatic cancer is poor; therefore, novel treatment approaches are needed. Clinical studies have demonstrated the efficacy of the targeted anticancer drug sotorasib in patients harboring a specific mutation in the KRAS protein, as well as the effectiveness of electrochemotherapy, in which the uptake of chemotherapeutic agents into cells is increased by electroporation, thereby improving treatment efficacy. In this master’s thesis, the cytotoxic effects of sotorasib, chemotherapeutic agents, and electrochemotherapy were investigated in two human pancreatic cancer cell lines, PANC-1 and MIA PaCa-2. The aim of the study was to determine whether the combination of electrochemotherapy and sotorasib would induce greater cytotoxicity than electrochemotherapy alone. Such an effect was confirmed in the MIA PaCa-2 cell line. Using Spector’s formula, the interaction was calculated to be additive. The MIA PaCa-2 cell line harbors the G12C mutation in the KRAS gene and was therefore susceptible to the KRAS inhibitor sotorasib. The concentration at which 50% of the cells were killed (IC50) was also determined. No citotoxic effect was observed in the PANC-1 cell line, which was attributed to the absence of the aforementioned mutation. Electrochemotherapy was performed using the established chemotherapeutic agents cisplatin and bleomycin. Cytotoxic effects were observed for both agents in both cell lines. Cell survival in both cell lines was significantly affected by the electric pulses alone. Cell shape and size were determined using microscopy and Fiji software, whereas cell growth and viability were assessed using the PrestoBlue metabolic assay and fluorescence measurements. PANC-1 cells were found to be larger and more heterogeneous than MIA PaCa-2 cells. A shorter doubling time and greater sensitivity were observed in the MIA PaCa-2 cell line.
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