Figure 6. Aurk and Plk inhibitors suppress proliferation of human SHH-associated MB.

(A, B) Cells from patient-derived xenografts of SHH-associated MB that are sensitive (DMB-012, panel A) or resistant (RCMB-018, panel B) to SHH antagonists were treated with DMSO (0.25%), LDE-225 (500 nM), or BI-2536 (500 nM). Cells were pulsed with ³H-Td after 48 hours and harvested for analysis of ³H-Td incorporation at 66 hours. In DMB-012, LDE-225 and BI-2536 significantly inhibited ³H incorporation compared to DMSO control (p < 0.01 based on paired two-tailed t-test). In RCMB-018, BI-2536 caused significant inhibition (p = 0.01), whereas LDE-225 did not (p = 0.89). (C) DMB-012 cells were cultured in the presence of LDE-225 (100 nM), PHA-739358 (100 nM) or the combination of LDE-225 + PHA-739358, and assayed for 3H–Td incorporation as described above. Data represent means of triplicate samples ± SEM. ³H-Td incorporation in the presence of LDE-225 + PHA-739358 was significantly lower than in the presence of LDE-225 alone (p = 0.05) or PHA-739358 alone (p = 0.004).