Fig. 8: Determinants of GNE/BMS synergy.
From: Synergistic targeting of cancer cells through simultaneous inhibition of key metabolic enzymes
After determination of sublethal drug concentrations of GNE and BMS, the indicated cell lines were treated for 3 days using the previously determined, cell line-specific, fixed sublethal concentration of BMS in combination with the full dose-titration of GNE. The effect of GNE/BMS combination on cell viability was determined by measuring the intracellular ATP content by ATP LiteTM. A GNE/BMS synergy was calculated using the Bliss independence model. The dotted line indicates the threshold of high Bliss synergy ( > 20). B Cell lines were grouped according to their tissue of origin and presented as boxplots. C Volcano plot showing the synergy behavior of combination treatment in relation to mutations in 38 known tumor-relevant genes (Supplementary Tables 3 and 4). D Volcano plot of Pearson correlations between GNE/BMS Bliss synergy scores and basal expression levels of 19,080 genes of 95 cell lines. Shown is a subset of cancer relevant genes. E The pre-ranked Pearson correlation list of 19,080 genes was subjected to GSEA using the KEGG database as the reference set. Depicted are the top 7 enriched pathways associated with either GNE/BMS resistance or sensitivity.
