Figure 3.
In vitro efficacy and mechanism of action of TTFields in combination with sorafenib. HepG2 and Huh-7D12 cells were treated for 72 h with various concentrations of sorafenib, alone or in combination with 150 kHz TTFields, followed by examination of cell count (a), overall effect (b), and apoptosis (c). Values are mean (N ≥ 3) ± SEM. For the dose effect of sorafenib: p < 0.001 for cell count and apoptosis, and p < 0.005 for overall effect. For the effect of TTFields versus sorafenib alone: p < 0.001 for cell count and overall effect, p < 0.01 and p = 0.16 for apoptosis assay live cells in HepG2 and Huh-7D12 cells, respectively; two-way ANOVA. HepG2 cells were treated for 6, 24, or 48 h with 150 kHz TTFields, 3 µM sorafenib, or the two treatments combined, followed by Western blot examination of the autophagy markers beclin-1 and LC3 (d), the ER stress marker GRP78 (e), and the apoptosis marker cleaved PARP (f). Values are mean (N ≥ 3) ± SEM. ** p < 0.01, *** p < 0.001, and **** p < 0.0001 relative to time-respective control; two-way ANOVA. ANOVA = analysis of variance; SEM = standard error of the mean; TTFields = Tumor Treating Fields.
