Fig. 7.

Impairing NB aggressive phenotypes with MIF and CXCR4 inhibitors. A) Cell viability after exposure to CM-CNT or CM-BM/NB and treatments (vehicle, 10 nM AMD3100 and 5 μM 4-IPP) at 72 h. Data is represented as a fold-change viability to time 0 h (n = 3). Significances were obtained after comparing vehicle vs treatments. One-way Anova Kruskal-Wallis test. B) Images (10x) and graph bar quantification of LAN-1 wound healing recovery under CM-CNT and CM-BM/NB normoxia and hypoxia (vehicle, 10 nM AMD3100 and 5 μM 4-IPP) at 24 h. Two-way Anova Sidaks’s multiple comparison test. C) Images and graph bars of invaded cells with 5 μM 4-IPP or 10 nM AMD3100, under CM-BM/NB normoxia (black) and hypoxia (blue) at 96 h. One-way Anova Kruskal-Wallis test. * P < 0.05. D) Cytotoxicity of chemotherapy compounds, doxorubicin and etoposide, in LAN-1 cells cultured with CM-BM/NB at 72 h together with 5 μM of 4-IPP or vehicle. Bar graph with relative viability at CM-BM/NB for doxorubicin and etoposide IC50. Normoxia (black), hypoxia (blue). Two-way Anova, Dunnett’s multiple comparison test. (n = 3) (*) P < 0.05. E) Individual tumor growth in vehicle and 4-IPP treated group. F) Tumor survival curves for each group. Events were reported when tumor size reached 1000 mm³. G) Body weight variation of mice during treatment (grey area) and follow-up