Therapeutic effects of combination therapy with sorafenib and everolimus in PTEN-deficient prostate cancer. PTEN-deficient mice with CNPC and CRPC were treated with sorafenib, everolimus or sorafenib plus everolimus for 4 weeks as described in the materials and methods (n = 8 mice/group). (A) Representative images of GUTs from mice after indicated treatment. Prostate tumors are highlighted in yellow. Scale is represented in mm. Plots of tumor burden assessed by tumor surface area for CPNC (B) and CRPC (C) intervention models. Plots of cellular proliferation rates relative to control mice assessed by the number of Ki67-positive/Ki67-negative cancer cells (D) and the cellular apoptotic rates relative to control mice assessed by the number of TUNEL-positive cells bodies/total negative cancer cells (E). All plot values represent the percent of control expressed as the mean ± s.e., *P < 0.05, **P < 0.001.