Fig. 8: Paxalisib and mirdametinib show selective effects on cell survival and proliferation in vivo. | Nature Communications

Fig. 8: Paxalisib and mirdametinib show selective effects on cell survival and proliferation in vivo.

From: Patient-derived models recapitulate heterogeneity of molecular signatures and drug response in pediatric high-grade glioma

Fig. 8

a Left: A single western blot of lysates from intracranial PDOX SJ-DIPGX37 (untreated, lane 1) and SJ-DIPGX7 (lanes 2–9) treated with vehicle (veh), paxalisib (pax, 12 mg/kg), mirdametinib (mir, 17 mg/kg), or the combination of paxalisib and mirdametinib (pax + mir) as indicated; antibodies are indicated at right. Quantification of IHC in sections from SJ-DIPGX7 tumors treated with agents shown along the x-axis for active caspase-3 (middle) and phospho-histone H3 (right), n = 3 tumors for veh, mir and n = 4 tumors for pax and pax + mir. The p values for comparison of active caspase-3 staining are veh vs. mir 0.9454, veh vs. pax 0.0964, veh vs. pax + mir 0.0032, mir vs. pax 0.0383, mir vs. pax + mir 0.0014, and pax vs. pax + mir 0.1474. The p values for comparison of p-H3 staining are veh vs. mir 0.7418, veh vs. pax 0.1733, veh vs. pax + mir 0.0258, mir vs. pax 0.6600, mir vs. pax + mir 0.1435, and pax vs. pax + mir 0.5747. b Left: IHC for pAKT Ser473 and pERK in SJ-DIPGX37 tumors in representative tumors treated with veh, pax, mir, or pax + mir as indicated. Quantification of IHC staining in sections from SJ-DIPGX37 tumors treated with agents shown along the x-axis for active caspase-3 (middle) and phospho-histone H3 (right), n = 3 tumors for each treatment. The p values for comparison of active caspase-3 staining are veh vs. mir 0.9628, veh vs. pax 0.9405, veh vs. pax + mir 0.0003, mir vs. pax 0.9997, mir vs. pax + mir 0.0005, and pax vs. pax + mir 0.0006. The p values for comparison of p-H3 staining are veh vs. mir < 0.0001, veh vs. pax 0.0110, veh vs. pax + mir < 0.0001, mir vs. pax 0.0043, mir vs. pax + mir 0.3352, and pax vs. pax + mir 0.0006. NS not significant; *p < 0.05; **p < 0.01; ***p < 0.001, ****p < 0.0001 using ordinary one-way ANOVA with post hoc Tukey test. The error bars indicate the mean ± s.d. Scale bar in b, left panel = 100 µm.

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