Drug combination effect
(A) Prostate cancer xenograft. 22Rv1 cells (7 × 106 cells) were injected subcutaneously into both flanks of nude mouse (5 mice/group). After tumors were established, mice were treated twice a week with 3 mg/kg DOX i.v. and 10 mg/kg gamitrinib i.p. as single agents or in combination. (B) Orthotopic xenograft of breast cancer cells. MDA-MB-231 cells (1 × 107 cells) were grown in mammary fat pads of nude mouse (3 mice/group). Mice were treated twice a week with 3 mg/kg DOX i.v. and 10 mg/Kg gamitrinib i.p. as single agents or in combination. (C) Hematoxylin and eosin staining of heart tissues. At the end of the experiment in (B), heart ventricles were collected from the mice and analyzed by hematoxylin and eosin staining. Magnification, 200×. (D) Serum creatine phosphokinase activity. Blood was drawn from mice at the end of experiments in (B) and serum creatine phosphokinase (CPK) activity was measured. n.s., p > 0.05. (E) JNK phosphorylation in tumor tissue. Tumor samples collected from the xenograft mice in (B) were analyzed by western blotting. (F) Accumulation of Bim and Bax in mitochondria. Mitochondrial fractionations isolated from the tumors in (B) were analyzed by western blotting.