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. 2018 Jun 19;14(6):e1006192. doi: 10.1371/journal.pcbi.1006192

Fig 4. Drug-mediated switch-like responses are linked to drug synergy.

Fig 4

(a-b) 3-dimensional (3D) simulations of the normalised steady-state pERK and pSTAT3 levels to simultaneous increases of Gefitinib and PF396 concentrations. The simulation shows a switch-like response pattern. Activation states of ERK and STAT3 were slightly suppressed upon single-drug treatments (blue dots), while the combined treatment significantly suppressed these activation states (red dots). (c) Experimental data of the effect of increasing concentrations of Gefitinib or PF396 for 24h on the protein levels and activation states of indicated signalling proteins. Shown are representative WB results of reproducible experiments of MDA-MB-468 cells. (d-e) 2D dose-response simulations of steady-state pERK and pSTAT3 levels to Gefitinib and PF396, respectively. (f-g) Quantification of experimental data in (c). (h-k) Cell proliferation dose-response curves of Gefitinib or PF396 treatment assessed by MTT assay in MDA-MB-468 and BT-20.