Fig. 3.

Treatment with 9-ING-41 enhances the antitumor effect of CPT-11 in breast BC-1 PDX (ER+/PR+/HER2−) tumors. (A) Treatment history of breast cancer patient (case BC-1). Breast PDX tumor model was established after orthotopic injection of metastatic pleural effusion cells (obtained from breast cancer patient) in NSG mouse. Breast PDX tumor pieces were re-transplanted orthotopically to 20 mice (1 tumor per mouse). Tumors were size matched and mice were randomized into 4 treatment groups: control (DMSO; n = 4 mice), CPT-11 (5 mg/kg, n = 5 mice), 9-ING-41 (70 mg/kg, n = 5 mice) and CPT-11 + 9-ING-41 (n = 5 mice). (B) Vehicle or drugs were injected as indicated by arrows. Points, mean tumor volume; bars, SE. (C) Weight of resected tumors was measured. Columns, mean tumor weight; bars, SE. (D) Representative pictures of PDX subQ tumors from each group of animals. (E) Representative pictures of GSK-3β, phospho-Glycogen Synthase and β-catenin expression in control and 9-ING-41-treated BC-1 PDX tumors.