Fig. 5

VDAC2 enables BAX-mediated killing of cancer cells in vitro and in vivo. a Deletion of VDAC2 inhibits BAX-mediated apoptosis in glioblastoma cells. Glioblastoma cells (U-251) were treated with ABT-737 (1 μM) and S63845 (1 μM) and cell death assessed after 24 h. Data are mean+/−SEM of three independent experiments. *p < 0.05 based on Student’s unpaired t-test. b Deletion of VDAC2 protects HCT116 colorectal cancer cells from apoptosis. HCT116 cells were treated with ABT-737 (5 μM), A1331852 (5 μM) or ABT-737 (5 μM) + actinomycin D (1 μM) for 24 h and cell death assessed. Data are mean+/−SEM of five independent experiments. c BAX or VDAC2 deletion renders RS4;11 acute lymphoblastic leukemia cells resistant to venetoclax or other chemotherapeutic agents. WT, BAX^−/− or VDAC2^−/− RS4;11 cells were treated with venetoclax, ABT-737 and standard-of-care chemotherapies (F-ara, etoposide, doxorubicin) or the BAX/BAK-independent stimulus Fas ligand (FasL) and cell viability assessed by PI exclusion. Data are mean+/−SEM of at least 3 independent experiments. d Deletion of VDAC2 renders RS4;11 cells resistant to venetoclax in vivo. RS4;11 cells were subcutaneously engrafted into NOD/SCID/IL-2Rγ^null mice, treated with venetoclax and tumor growth monitored by IVIS imaging. The collated data (top panel) is normalized to represent relative tumor burden. Data are mean+/− SEM collated from four independent experiments, N = 12 mice engrafted with each genotype of RS4;11 cells