Fig. 7

Therapeutic susceptibility of Rasa1-deficient gastric cancer (GC) to Bcl-xL inhibition. A and B Sphere-forming assay of control and Rasa1-KO S1 cells treated with BH3I-1 (25 µM) and/or venetoclax (5 µM). A Size and number of tumorspheres and (B) representative images of control and Rasa1-KO tumorspheres after BH3I-1 treatment. P value, Student’s T test. C and D Dose–response curve of relative cell viability after 5 days of treatment with BH3I-1 (C) and venetoclax (D) at the indicated concentrations in control and Rasa1-KO S1 tumorspheres using ATP cell viability luciferase assay. P value, Student’s T test. E Sphere-forming assay using SNU-484 and MKN-74 human GC cells treated with BH3I-1 at the indicated concentrations for 5 days. (left) Tumorsphere size and number and (right) representative images of SNU-484 (top) and MKN-74 (bottom) tumorspheres treated with vehicle and BH3I-1. P value, Student’s T test. F and G Sphere-forming assay using control and Rasa1-KO SNU-719 (F) and NCI-N87 (G) cells treated with BH3I-1 at the indicated concentrations for 5 days. The graph indicates the size (top) and number (bottom) of tumorspheres. P value, Student’s T test. H and I Effect of Bcl-xL inhibition on peritoneal dissemination was evaluated by intraperitoneally injecting control or Rasa1-KO S1M cells into NOD-SCID mice and treated with vehicle and A-1155463 (5 mg/kg, i.p., once daily) for 10 consecutive days. H Representative images of closed and opened peritoneum for each group. I Ascites volume (top) and number of macro-metastatic foci in each group (bottom) at the time of necropsy. P value, Student’s T test