Fig. 6.

BMI1 inhibitor (PTC596) is effective against the mesenchymal subgroup of glioblastoma (GBM). a-c Cell viability (a), tumorsphere formation (b), and foci formation (c) was determined for proneural (PN12) and mesenchymal (MES23) glioma stem cells (GSCs) transfected with the indicated plasmids in the presence or absence of PTC596 (10 μM) treatment for 24 h (a), 72 h (b), or 2 weeks (c) . Data are presented as means ± SEM (*, p < 0.05; ***, p < 0.001). d Kaplan–Meier survival curve showing the survival of NOD SCID gamma mice injected with 500 PN12 or 500 MES23 (or shRNA-ZDHHC18 MES23) GSCs with or without PTC596 treatment (n = 15; *, p < 0.05; ***, p < 0.001). e Immunohistochemistry analysis for H2AK119Ub and Ki-67 in sections from the xenografts of intracranially implanted PN12 GSCs. Quantification of H2AK119Ub and Ki67 positive cells in three fields is presented. Error bars represent the SEM (ns, not significant). Scale bar, 200 μm. f Immunohistochemistry analysis for HIF1α and H2AK119Ub in sections from the xenografts of intracranially implanted PN12 GSCs. Blue box, hypoxic region; red box, normoxic region. Scale bar: (left image) 500 μm; (right image, inset box) 100 μm (white). Quantification of HIF1α and H2AK119Ub positive cells in three fields is presented. Error bars represent the SEM (***, p < 0.001). g Immunohistochemistry analysis for H2AK119Ub and Ki-67 in sections from the xenografts of intracranially implanted MES23 GSCs transfected with the indicated plasmids with or without PTC596 treatment. Quantification of H2AK119Ub and Ki67 positive cells in three fields is presented. Error bars represent the SEM (***, p < 0.001). Scale bar, 200 μm