Figure 7
Combinatorial treatment of mice bearing aggressive androgen-insensitive tumors with both SB203580 and Enzalutamide, results in significant regression of primary tumor formation as well as marked loss of circulating tumor cell population. (a) Schematic shows the design for in vivo experiments. (b) Quantification of luminescence of luciferase activity in tumors formed by DU145–RFP–Luciferase-labeled cells, and treated as indicated. (c) Tumors isolated from mice treated as indicated (scale bar,1 cm, n=8 data points). (d and e). Graphs show tumor volume (d) and tumor weight (e), respectively, in indicated conditions (NS=P>0.05, **P<0.01). (f) qRT–PCR analyses for FOXC2, and other indicated markers in isolated tumors. Y-axis represents fold change in HPRT-normalized mRNA expression in randomly selected tumor samples compared with that in pooled control vehicle-treated tumors (n=3; error bars indicate s.e.m.). (g) IHC for FOXC2, AR and pATF2 (a marker for activated p38 signaling) on indicated tumors. (h) Quantification of colonies formed by CTCs isolated from blood of mice bearing various tumors as indicated. The colonies were confirmed to be of human origin by RFP expression that was stably introduced into DU145 cells (NS=P>0.05, ***P<0.001). (i) Schematic depiction of the participation of FOXC2 in the reprogramming of differentiated/epithelial PCa cells into ADT-insensitive, drug-resistant/neuroendocrine stem-like cells lacking epithelial traits. NS, not significant.
