Figure 4.

Effects of IL-6 signaling blockade on activity of the AKT-mTOR pathway after (A) sorafenib, (B) sunitinib or (C) pazopanib treatment. Influence of tocilizumab (50 μg/ml) on activation of AKT-mTOR pathway in 786-O cells after treatment with TKI was determined by Western blot. The concentrations of TKIs are indicated on the X axis of each graph. In combinational treatment (right part of each graph) tocilizumab was used in a concentration of 50 μg/ml. The column labeled by 0 μg/ml in the right part of each graph represents treatment with tocilizumab alone. Phosphorylation of AKT, mTOR, 4EBP1, S6RP, NFκB, and STAT3 was enhanced after TKI treatment at concentration of 0.5 μM. HIF-2α was enhanced by treatment with TKIs in all concentrations used. Tocilizumab neutralized these effects. The results are presented as the relative mean value ± standard deviation of three independent analyses, each in triplicate, related to untreated control cells. *p < 0.05 compared with the control cells.