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. 2020 Nov 20;10:554704. doi: 10.3389/fonc.2020.554704

Figure 5.

Figure 5

Pan HER targeting sensitizes Basal type but not Claudin type Triple Negative Breast Cancer (TNBC) cells to AKT and PI3K inhibition. (A) Biochemical assessment of downstream signaling in the PI3K/AKT signaling pathway after combination therapy with neratinib (300 nM) and GDC0068 (1 uM) or GDC0077 (1 uM) after 48 h, showing deceased signaling in the Basal TNBC cell lines but not in the Claudin type TNBC. (B) Viability assay of TNBC cells treated with the small molecule inhibitors GDC0068, GDC0077, neratinib, or a combination of the drugs for 96h [drug treatments as in (A)]. In the BT-20, HCC-70, and MDA-MB-468 cell lines, combination therapy demonstrated decreased viability compared to the MDA-MB-231and BT-549 cell line which showed no added benefit of combination therapy. Drug response graphs show CellTiter-Glo luminescence viability measurements at the end of the experiments compared to untreated control and analyzed using two-way analysis of variance (ANOVA)/Tukey’s multiple comparison test, *<0.05, **P < 0.01, ***P<0.001]. Experiments were performed in triplicate. Data are means ± SD].