Figure 5
From: The impact of S6K1 kinase on neuroblastoma cell proliferation is independent of GLI1 signaling
Combination of small molecule inhibitors of GLI and PI3K/mTOR do not cooperate in inducing the suppression of neuroblastoma cell growth. Dose–response curves for GANT61 cytotoxicity, in combination with the PI3K/mTOR inhibitors AR-12, CCI-779 and NVP-BEZ 235, in SK-N-AS and SK-N-BE(2) cells treated for 72 h. The PI3K/mTOR inhibitors were tested in the following concentration spans: AR-12: 2 μM - 0.0078 μM, CCI-779: 20 μM – 0.078 μM and NVP-BEZ235: 0.4 μM - 0.0016 μM. A fixed ratio of GANT61 to the PI3K/mTOR inhibitors was used in the combination experiments (GANT61:AR-12 20:1; GANT61:CCI-779 2:1 and GANT61:NVP-BEZ235 100:1). Note that no additive or synergistic effects are seen in the combinatorial treatments except for the GANT61/CCI-779 combination in SK-N-BE(2) cells. This may relate to high concentration of CC1-779 used compared to the other PI3K/mTOR inhibitors, which could elicit non-specific effects in this cellular context.