Fig. 5: Cetuximab-resistant HNSCC cells rely on the availability and utilization of exogenous FA for their growth in vitro and in vivo.

a Growth of cetuximab-sensitive (-S) and resistant (-R) FaDu cells upon transfection of siRNA against CD36 for 72 h (N = 3, n = 3). Growth of cetuximab-resistant (-R) FaDu (b) and SC263 cells (c) upon treatment with 1 µg/ml cetuximab for 72 h, in a medium supplemented with normal or delipidated FBS (N = 3, n = 3). Growth of FaDu-R (d) and SC263-R cells (e) upon treatment with 1 µg/ml cetuximab for 72 h, in a delipidated FBS-containing medium supplemented with 1% chemically defined lipid concentrate (LC) or a mix of BSA-conjugated palmitate and oleate (50 µM of each FA) (N = 3, n = 6). Growth of cetuximab-sensitive FaDu cells upon incubation up to 6 weeks with 1 µg/mL cetuximab in full or lipid-depleted culture medium (f) and comparison of cell viability at 1 week and 6 weeks of cetuximab treatment (g) (N = 2, n = 3). Growth of cetuximab-sensitive (-S) and -resistant (-R) FaDu cells in 2D (h) and 3D conditions (i) upon treatment with 100 µM etomoxir for 3 or 14 days respectively (N = 3, n = 3). j Volume at day 17 of in vivo tumor xenografts from FaDu-R cells in nude mice daily treated with 40 mg/kg etomoxir (or DMSO as vehicle) alone or in combination with 30 mg/kg cetuximab (or 0.9% NaCl as vehicle) (N = 6). Data are plotted as the means ± SEM. N indicates the number of independent biological experiments and n indicates the number of technical replicates (when >1). Significance was determined by two-way ANOVA with Sidák’s multiple comparison test (a–e, h and j). P-values as indicated or ***P < 0.001; ns not significant. Source data are provided as a Source Data file.