Recapitulation of Tumor Heterogeneity and Molecular Signatures in a 3D Brain Cancer Model with Decreased Sensitivity to Histone Deacetylase Inhibition
Figure 7
RCCS glioblastoma aggregates demonstrate reduced drug sensitivity.
U87 and KNS42 glioblastoma cultures (monolayer or RCCS) were treated with Vorinostat for 72 hours prior to assessment of proliferation using the Alamar Blue assay. A – U87 2D cells show dose-dependent sensitivity to Vorinostat with an IC50 ∼5 µM. B – U87 aggregates generated using the RCCS are less sensitive to Vorinostat with an IC50 ∼12.5 µM. C – KNS42 2D cells show acute sensitivity to Vorinostat with an IC50 ∼1 µM. D – KNS42 aggregates generated using the RCCS are markedly less sensitive to Vorinostat in comparison with an IC50 ∼13.5 µM. E – Mean IC50 values calculated from A–D. Drug treatment data on 2D monolayer cultures are expressed as percentage viability relative to untreated cultures and presented as the mean of three independent experiments with standard error of mean shown. Drug treatment data on 3D aggregates are presented as the mean of two independent experiments that are normalized to Alamar Blue readings of each culture immediately prior to drug exposure with standard error of mean shown.