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. Author manuscript; available in PMC: 2019 Aug 1.
Published in final edited form as: Cancer Res. 2018 May 29;78(15):4360–4369. doi: 10.1158/0008-5472.CAN-17-3124

Figure 1. The combination of CDK4/6 and c-Met/Trk inhibition is synergistic against GBM.

Figure 1

(A–B) Abemaciclib treatment increases the phosphorylation of c-Met, TrkA, and TrkB which is reversed by altiratinib. Shown is an antibody array (ELISA) (*P < 0.05; two-tailed t-test) and an immunoblot using antibodies specific for Met and Trk. Protein expressions were quantitated and plotted (***P < 0.0001). (C) GIC lines show sensitivity to both abemaciclib and altiratinib in a dose-dependent manner (**P < 0.01; ***P < 0.0001; one-way analysis of variance (ANOVA) with post-hoc Tukey analysis). (D) Dose-effect curve generated with the Chou-Talalay method using the CompuSyn program. Combination index (CI) less than 0.2 indicates strong synergy. CI values for G88 and G528 are 0.05 and 0.1, respectively. (E) Self-renewal assay. 10 and 100 GICs were plated in 24-well plates and cultured as floating cells over two weeks to compare sphere formation upon treatment with vehicle, abemaciclib (1 μM), altiratinib (2.5 μM), and the combination of abemaciclib and altiratinib (*P < 0.05; ***P < 0.0001; ANOVA with post-hoc Tukey analysis).

(Abe: Abemaciclib, Alti: Altiratinib. NS: Not significant. All values are mean ± SEM and from three biologically independent samples. Cell viabilities were determined via cell counts following three days of treatment. Each experiment was performed three times using separate samples).