Figure 5. Survivin antagonists cooperate with radiation and LDE225 SHH antagonists.

A) Tumor cells were treated with either 0.1% DMSO, 50 nM YM155, or 10 μg/ml S12 for 24 hr, and then irradiated with 0, 0.25, or 0.5 gray (Gy). After 24 hr, cells were pulsed with ³H-thymidine and assayed for incorporation. Treatment with antagonists enhanced sensitivity of tumor cells to radiation (p<0.02 for all treatments, calculated by 2 way ANOVA to identify radiation dose by treatment interaction, split by radiation dose, with post hoc student's t-tests) Data are representative of 5 experiments. (B,C) Tumor cells were plated in 96 well plates and treated with LDE225 alone (at the indicated concentrations) or in combination with 20 nM YM155 (B) or 10 μg/ml S12 (C). Cells were pulsed with ³H-thymidine after 48 hr and harvested to assay levels of incorporation. Combination treatment of LDE with either S12 or YM155 significantly lowered the IC50 compared to LDE alone (p< 0.01 by student's t-test). Data are representative of 4 (B) and 3 (C) experiments. All data represent mean +/- SD.