Figure 1

AR enhances sorafenib efficacy to suppress HCC invasion via AR-pSTAT3/pAKT/pERK pathway. (a) Chamber-transwell invasion assays showed that overexpression of AR decreased the cell invasion in HepG2 and SKhep1 cells under 48 h sorafenib (5 μM) treatment. Left panel, representative images of the chamber-transwell invasion assays; right panel, quantification of the invaded cells. The invaded cells were counted in 10 randomly chosen microscopic fields (× 100) of each experiment and pooled. (b) 3D invasion assays on HepG2 and SKhep1 cells showed that overexpression of AR could significantly decrease the invasion ability under 48 h sorafenib (5 μM) treatment. The cells with protrusions were regarded as invaded cells and 10 random different fields at × 200 magnification were counted for quantification. (c) Disease-free survival (DFS) curve of HCC patients (N=364) from TCGA project indicated that patients with higher AR expression (defined by RNA sequencing with group cutoff in median) had significant better disease-free survival (HR=0.71) than patients lower AR expression. (d) Disease-free survival (DFS) curve of HCC patients (N=182) indicated that patients with higher AR expression (defined by RNA sequencing with group cutoff in 75%/25% quartile) had significant better disease-free survival (HR=0.53) than patients lower AR expression. (e) Sub-stage-dependent analysis suggested lower AR expression in later stages of HCC patients from TCGA project. (f) Major-stage-dependent analysis lower AR expression in later stages of HCC patients from TCGA project. (g) Western blot assays were used to test downstream altered molecules upon 5 μM treatment in SKhep1 and HA22T cells. (h) Western blot assays were used to test downstream altered molecules upon overexpressing AR in SKhep1 and HA22T cells under 48 h sorafenib treatment. P<0.05 was considered statistically significant. * P<0.05 and *** P<0.001