Figure 5 from Attenuating Adaptive VEGF-A and IL8 Signaling Restores Durable Tumor Control in AR Antagonist–Treated Prostate Cancers

Inhibition of VEGF and IL8 enhances tumor sensitivity to enzalutamide in vivo. For all experiments, male Balb/c SCID mice bearing tumors of 100 to 150 mm3 were assigned to the following treatment groups for 28 days: Vehicle; enzalutamide (Enz; 4 mg/kg) + IgG control (150 μg/mL); Vehicle + anti-VEGF nAb (100 μg/mL) and anti-IL8 (50 μg/mL) nAbs; and Enz (4 mg/mL) + anti-VEGF (100 μg/mL), and anti-IL8 (50 μg/mL) nAbs. A and B, Tumor growth data, obtained by measuring (A) LNCaP-PAR and (B) LNCaP-EnzR tumor volume every 2 days. The treatment schematic is shown above the graph. The data points represent the mean ± SD (N = 8/group). C and D, Normalized bodyweight (at end of treatment) of mice with (C) LNCaP-PAR and (D) LNCaP-EnzR tumors treated with Enz alone or in combination with anti-VEGF nAb and anti-IL8 nAb. Values shown are mean ± SD (N = 8/group). E and F, Intratumoral oxygenation concentration (mmHg) in (E) LNCaP-Par and (F) LNCaP-EnzR in vivo tumors (N = 4/group) treated with Enz alone or in combination with anti-VEGF nAb and anti-IL8 nAb for 29 days and measured time-dependent changes. For all experiments, statistical analysis was carried out using a 2-way ANOVA with Tukey post-hoc test: *, P < 0.05; **, P < 0.01; ***, P < 0.001.