Figure 7. PN and MES GBM subtypes can be selectively inhibited with pathway-specific inhibitors.

(a) Sphere formation and cell proliferation of indicated glioma spheres treated with DMSO (Ctrl), KN93 (5 μM), 5Z-7-oxo (5 μM), BAY-117082 (5 μM), JSI-124 (0.1 μM), LGK974 (5 μM), ICG-001 (5 μM), or LGK974 (5 μM)+Wnt3a (200 ng ml⁻¹), respectively. (b) Summary of data shown in Supplementary Fig. 11. An overview of knockdown of β-catenin (CTNNB1), TCF4, CaMK II, TAK1, NF-κB, STAT3, or NLK that reduce proliferation and self-renewal abilities of PN and MES spheres. Data were normalized to the control. *Relative inhibitory effects on indicated protein expression or cellular properties. *P<0.05, **P<0.01, ***P<0.001. (c) Effects of Wnt inhibitor LGK974 (3 mg kg⁻¹) and NF-κB inhibitor Bay-117082 (10 mg kg⁻¹) on tumour xenografts established subcutaneously by PN 23 or MES 83 spheres. Indicated glioma spheres (1 × 10⁶ cells) were implanted into the flanks of nude mice. Treatments were started when palpable tumours appeared. Representative bioluminescent images (left) are shown. (d) Dissected flank tumours (upper) and tumour growth kinetics (lower) from different groups are shown. Error bars (s.d.) represent the data of triplicate samples for each cell line or tumours from five individual mice in each group. *P<0.05, **P<0.01, ***P<0.001, paired two-way Student's t-test. Data are representative from three independent experiments with similar results.