Therapeutic Effects of Ethyl Pyruvate on Tumor Growth and Metastasis in a Severe Combined Immunodeficiency Mouse Orthotopic Implantation Model

Abstract

Ethyl pyruvate (EP) has been shown to have significant anti-inflammatory activities. Here, we explore the therapeutic effects of EP administration on tumor growth and metastasis in orthotopic implantation human gastric cancer models in severe combined immunodeficiency (SCID) mice. After SCID mice were treated with EP, the tumor growth and liver metastasis from gastric cancer were investigated and its possible molecular mechanisms were further studied. As a result, it was found that EP could inhibit tumor growth and liver metastasis of gastric cancer, and reduce tumor lymphangiogenesis indicated by lymphatic microvessel density (LVD) in gastric cancer and metastatic liver tumor. Also, EP decreased the expression of high mobility group box-B1 (HMGB1), receptor for advanced glycation endproducts (RAGE), vascular endothelial growth factor (VEGF) and membrane type-1 matrix metalloprotease (MT1-MMP) in gastric cancer and metastatic liver tumor, but it exerted no effect on expression of nuclear factor-kappa B (NF-κB). Taken together, we suggest that the new application of EP could be a therapeutic option in the treatment of gastric cancer and metastatic liver tumor.