Inhibition of MDM2 via Nutlin-3A: A Potential Therapeutic Approach for Pleural Mesotheliomas with MDM2-Induced Inactivation of Wild-Type P53

Figure 4

Figure 4 shows boxplots for apoptosis for the investigated MPM cell lines. On the y-axis RLU (relative luminescence units) are shown. RLU and increasing apoptosis rates show a direct correlation. On the X-axis, the concentrations of the cytostatics applied and the control are shown. For cell line NCI-H2052 and NCI-H2452 (shown in Figures 4(a) and 4(c), respectively), 20μM Nutlin-3A showed the strongest induction of apoptosis when comparing single agents (cisplatin: NCI-H2052: p=0.084, NCI-H2452: p=0.028; pemetrexed: NCI-H2052: p=0.011, NCI-H2452: p=0.049) but also against cisplatin combined with pemetrexed (NCI-H2052: p=0.015, NCI-H2452: p=0.008). MSTO-211H (shown in Figure 4(b)), the highest apoptosis rate, was found for pemetrexed followed by 5μM, 20μM Nutlin-3A, and the combination of pemetrexed and cisplatin (all p<0.001). When analyzing Nutlin-3A in combination with cisplatin, for cell line NCI-H2052, (a) the highest apoptosis rate was found for 10μM Nutlin-3A combined with cisplatin (all p<0.001). MSTO-211H (b) apoptotic rates of 10μM Nutlin-3A combined with cisplatin comparable to the treatment with pemetrexed alone (p=0.493) significantly enhanced against all other approaches (p=0.016). In NCI-H2452 (c), treatment with cisplatin combined with 20μM and 10μM Nutlin3A showed the strongest induction of apoptosis beside 20μM Nutlin-3A alone (p=0.004) but shows no statistically significant differences compared with 20μM Nutlin-3A single agent treatment (p=0.199).

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