Fig. 4.

Western blot analysis of EGFR signaling components in OSCC cell lines treated for six hours with Gefitinib (500 nM), TAE684(500 nM), or both. Panel A: HSC3 cells treated with Gefitinib demonstrate a reduced ratio of phosphorylated EGFR (p-EGFR) to total EGFR. An additive reduction of p-EGFR/EGFR is seen with a combination treatment (Combo) of TAE684 and Gefitinib. The ratio of phosphorylated AKT (p-AKT) to total AKT is significantly reduces with individual treatments and abolished with combination treatments. No change in the ratio of phosphorylated ERK1/2 (p-ERK1/2) to total ERK1/2 is seen. Lone treatment with the ALK inhibitor, TAE684, significantly induces activation of STAT3 as reflected in the ratio of phosphorylated STAT3 (p-STAT3) to total STAT3. This induction is reversed with combination treatments of TAE684 and Gefitinib. Panel B: Cal27 cells treated with Gefitinib demonstrate no significant changes in the ratio of p-EGFR to total EGFR. Gefitinib alone abolished p-AKT and TAE684 alone significantly reduced the ratio of p-AKT to total AKT. Similarly, combination treatment of Gefitinib and TAE684 (Combo) abolished p-AKT and no change in the ratio of p-ERK1/2 to total ERK1/2 is seen in Cal27 cells. Although a trend is seen with an increase in the p-STAT3 to total STAT3 ratio is seen with all treatments, no significant changes were detected. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001 denote significance between treatments.