Establishing a peritoneal dissemination xenograft mouse model for survival outcome assessment of experimental gastric cancer

Abstract

BackgroundPeritoneal dissemination of gastric cancer is a common reason for unresectability, a frequent recurrence mechanism, and a common cause for death. The present study was performed to test peritoneal dissemination gastric cancer xenografts mouse models that would support survival outcome analyses. Materials and methodsHuman gastric cancer cell lines AGS, NCI-N87, and SNU-16 were intraperitoneally injected into nude mice and severe combined immunodeficiency (SCID) mice. The peritoneal tumor formation and mouse survival were compared among different groups. Mice were treated with oxaliplatin (5 mg/kg) and NVP-BEZ235 (10 mg/kg). ResultsThe formation rate of peritoneal cancer after intraperitoneal injection of 5 × 106 SNU16, NCI-N87, and AGS cells was 2/8, 6/8, and 0/8 in nude mice, and 6/6, 6/6, and 0/6 in SCID mice, respectively. Median animal survival with peritoneal dissemination was 74 d for NCI-N87 cells (10 × 106), 95 d for SNU16 cells (10 × 106), 78 d for SNU16 cells (20 × 106), and 44 d for SNU16 cells (40 × 106). In a therapeutic experiment with 40 × 106 SNU16 cells, animal survival was significantly improved by oxaliplatin treatment compared with the control group (58.5 d versus 45 d, P < 0.001), but not by NVP-BEZ235 (48 d versus 45 d, P = 0.249) treatment. In the accompanying subcutaneous SNU16 mouse model, relative tumor volume compared with controls was not significantly decreased by oxaliplatin treatment (P = 0.151) but by NVP-BEZ235 therapy (P = 0.008). ConclusionsPeritoneal gastric cancer xenografts were successfully established after intraperitoneal injection NCI-N87 and SNU16 cells. These findings provide a useful survival outcome assessment model for experimental gastric cancer research.