Figure 7.

Inhibition of Bcl-2 and Bcl-xL improved apoptosis induction in response to irradiation and downregulation of Mcl-1. (a) A172, U373, Ln229, and T98G cells were irradiated (0 Gy, 10 Gy) and treated with the Bcl-2/Bcl-xL inhibitor ABT737 (0 μM/solvent control, 1, 4, or 10 μM) immediately after irradiation. DNA fragmentation was analyzed 48 h after irradiation and treatment. IR increased ABT737-induced apoptosis in all glioblastoma cells, but to a greater extent in U373 and T98G than in A172 and Ln229 cells. Flow cytometric data show mean values±S.D. (A172, U373: n=6; Ln229, T98G: n=3). (b) A172, U373, Ln229, and T98G cells were transfected with 50 nM Mcl-1 (mcl1) siRNA or the respective non-targeting (nt) siRNA. After 24 h of transfection, cells were treated with ABT737 (0 μM/solvent control, 0.4, 1, or 4 μM). After 48 h, DNA fragmentation was analyzed by flow cytometry. Mcl-1 knockdown facilitates ABT737-induced apoptosis in A172 and Ln229 cells to a similar extent as in U373 and T98G cells. Flow cytometric data show mean values±S.D. (n=3). Significance was calculated to the respective non-irradiated cells. *P<0.05, **P<0.01, ***P<0.001