Fig. 2

Pharmacological FGFR/β1 integrin inhibition plus Cisplatin induces a broad, sensitizing-to-resistant viability spectrum in irradiated 3D HNSCC cell models. A Workflow of drug cell viability screen in 3D lrECM HNSCC cell models upon treatment using anti-β1-integrin mAb (AIIB2; 20 µg/ml), pan-FGFR inhibitor (Erdafitinib, FGFRi; 2 µM) and Cisplatin (CDDP; 0.5 µM) with or without single 6 Gy X-ray irradiation. Images were partly adapted from Servier Medical Art by Servier, licensed under a Creative Commons Attribution 3.0 Unported License. B Enhancement ratios (ER) of cell viability responses of indicated cell models to single, double and triple applications of AIIB2, FGFRi and CDDP. DMSO/IgG were used as controls. ER and statistics are derived from the corresponding cell viability data (Fig. S3A) and presented as mean ± range (n = 3, two-way ANOVA, Dunnett’s multiple comparison test to corresponding controls). C ER of cell viability responses of indicated 6 Gy X-ray irradiated cell models to single, double and triple applications of AIIB2, FGFRi and CDDP. DMSO/IgG were used as control. ER and statistics are derived from the corresponding cell viability data (Fig. S3B) and presented as mean ± range (n = 3; two-way ANOVA; Dunnett’s multiple comparison test to corresponding irradiated controls). D ER of cell viability responses of 20 indicated cell models comparing the triple combination AIIB2, FGFRi and CDDP to the corresponding single CDDP treatments with a single dose of 6 Gy X-ray irradiation. The adapted ER (AIIB2/FGFRi/CDDP vs. CDDP) and statistics are derived from corresponding cell viability data (Fig. S3D) and presented as mean ± range (Two-way ANOVA; Tukey multiple comparison test; ***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05, n.s. p > 0.05). E ER of cell viability responses of indicated cell models to the single, double or triple combination with AIIB2, FGFRi and CDDP. DMSO/IgG were used as control. ER and statistics are derived from the corresponding cell viability data (Fig. S4A) and presented as mean ± range (n = 3; two-way ANOVA; Dunnett’s multiple comparison test to corresponding controls). F ER of cell viability responses of indicated cell models to the single, double or triple combination of AIIB2, FGFRi and CDDP plus 6 Gy X-ray irradiation. DMSO/IgG were used as control. ER and statistics are derived from the corresponding cell viability data (Fig. S4B) and presented as mean ± range (n = 3; two-way ANOVA; Dunnett’s multiple comparison test to corresponding irradiated controls)