Hanne Verswyvel

Chapter 3 │ Page 83 At 24 hours, NTP already induced a significant decrease in viability across all cell lines, which also confirmed its strong cytotoxic potential (Figure 2A, C, E). In contrast, both CDDP concentrations led to only a modest reduction in spheroid viability. When combined with NTP, cytotoxicity of CDDP was significantly enhanced throughout all cell lines (CDDPlow vs COMBOlow, p ≤ 0.0007; CDDPhigh vs COMBOhigh, p ≤ 0,047). Two days post-treatment, the cytotoxic e ects became even more pronounced. While monotherapy NTP did not induce a substantial additional decrease compared to the levels at 24 hours, the highest concentration of CDDP led to a more pronounced viability reduction at this time point, highlighting the distinct timing of e ect penetrance between the two treatments [34, 36, 41]. However, the key finding here is that NTP still improved the e icacy of CDDP, illustrated by a significantly lower cell viability in the combination therapies compared to both monotherapies (Figure 2B, D, F). This e ect was observed across cell lines, suggesting that NTP did not only provide an immediate cytotoxic response but also enhanced the e ectiveness of CDDP at a subsequent stage. Building further on this significant reduction, we aimed to investigate the strength of this e ect by determining the potential synergy between the two agents. We opted for the Bliss Synergy Score Calculation method, suited for two therapies that independently act via di erent working mechanisms, in which scores between -10 and +10 demonstrate an additive e ect and scores above 10 stand for synergy between compounds [42]. Our analysis showed that the NTP-CDDP combined application provoked a strong additive e ect in Cal27 and SCC61 spheroids (Figure 3), underlined by scores ranging between -3.56 and 7.22 for both time points. The strongest e ect was observed for the SCC22B cells in which two out of the four combination options reveal a synergistic score (11.19 for COMBOlow at 24 hours, and 17.43 for COMBOhigh at 48 hours).

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