Inhibitory Effect of Ethyl Pyruvate on Orthotopic Transplantation of Gastric Cancer in Severe Combined Immunodeficiency Mice

Objective: To investigate the inhibitory effect and mechanism of ethyl pyruvate (EP) on the growth and liver metastasis of orthotopically transplanted gastric cancer in severe combined immunodeficiency (SCID) mice. Methods: SCID mice were orthotopically transplanted with SGC-7901 human gastric cancer tissue to establish a liver metastasis model of gastric cancer. Animals were injected intraperitoneally with different concentrations of EP. After 30 days, gastric cancer and metastatic liver tissues were taken out to detect the volume and weight of gastric cancer tissues and the number of metastatic liver nodules. Real-time quantitative PCR and immunohistochemistry were used to detect high mobility group protein B in different groups. Expression levels of 1 (HMGB1), receptor glycation end product receptor (RAGE), NF-κB, vascular endothelial growth factor (VEGF), and membrane type 1 matrix metalloproteinase (MT1-MMP). Results: Compared with the control group, the weight and size of gastric cancer tissue and the number of metastatic liver nodules in the EP treatment group were significantly reduced (P<0.01). EP inhibited the expression of HMGB1, RAGE, VEGF and MT1-MMP in gastric cancer and metastatic liver tissue, but had no significant effect on NF-κB expression. Conclusion: EP may inhibit the growth of gastric cancer and liver metastasis in SCID mice by down-regulating HMGB1-RAGE pathway, which may have therapeutic effects on cancer