Significant apoptosis effects were observed with the combination treatment of regorafenib with TMZ. Four GBM cells are treated with 10 μM regorafenib, 10 μM PD98059, 0.5 μM QNZ alone, or combined with 120 μM TMZ for 24 h. Cells are then detected A–B the activation of cleaved caspase-3, C–G the populations of subG1 phase and the activation of annexin V/PI, H–K the activation of Fas and Fas-L, L–M the activation of cleaved caspase-8, N–O the loss of the mitochondrial membrane potential (MMP) and P–Q the change of cleaved PARP-1 expression by flow cytometry. (a1
p < 0.05, a2
p < 0.01 vs. CTRL; b2
p < 0.01 vs. 120 μM TMZ)