Figure 1.

NVP-BKM120 inhibits glioma cell proliferation. A, structure of NVP-BKM120. B, waterfall plot of IC50 micromolar values. These graphs show that NVP-BKM120 has a particular growth inhibition signature, with some cell lines being exquisitely sensitive and others being relatively resistant. For this, glioma cell lines were plated in 96-well plates at a density of 5,000 cells per well. Cells were treated with increasing concentrations of NVP-BKM120 in triplicate wells for 72 hours, and cell viability was assessed by CellTiter-Blue assay as described in Materials and Methods. The results shown are of a single experiment with 3 independent replicates. C, the relative sensitivity of GBM cell lines to the PI3K inhibitor NVP-BKM120 versus p53 and PTEN status. The sensitivity of NVP-BKM120 against the GBM cell lines measured using CellTiter-Blue assay. Indicated values represent the concentration causing 50% growth inhibition (IC₅₀). Values are expressed relative to the mean of IC₅₀ of LN751 cell line using the equation: −log₂ (IC₅₀ individual cell line/IC₅₀ of LN751). D, dot blot showing correlation between p53 and PTEN status and in vitro drug sensitivity as shown by the IC₅₀ of individual cell line. Lines indicate median value. The wild-type p53 cells are more sensitive to NVP-BKM120 than p53-mutant/deleted glioma cells (P < 0.0001).