Abstract

BACKGROUND: Ginkgo biloba extract (EGb761), a standard extract of the Chinese traditional medicine Ginkgo biloba, plays an anti-tumor role in various cancers. However, whether EGb761 is involved in the invasion and metastasis of gastric cancer remains unclear.

MATERIAL AND METHODS: In the current study, cell viability assay, Western blotting, wound-healing assay, Transwell invasion assay, and orthotopic transplantation model were performed to explore the effects of EGb761 on gastric cancer.

RESULTS: In vitro, the results showed that EGb761 suppressed the proliferation of gastric cancer cells in a dose-dependent manner. Furthermore, the migration and invasiveness were weakened and the protein levels of p-ERK1/2, NF-κB P65, NF-κB p-P65, and MMP2 were decreased by EGb761 or U0126 (an inhibitor of ERK signaling pathway) exposure in gastric cancer cells. Moreover, the combined treatment with EGb761 and U0126 significantly inhibited ERK, NF-κB signaling pathway, and the expression of MMP2 than those of single drug. In vivo, EGb761 inhibited the tumor growth and hepatic metastasis of gastric cancer in the mouse model. Results of immunohistochemistry indicated that the expression of ERK1/2, NF-κB P65 and MMP2 were decreased by EGb761 in the tumor tissues.

CONCLUSIONS: EGb761 plays a vital role in the suppression of metastasis and ERK/NF-κB signaling pathway in gastric cancer.

Keywords: Extracellular Signal-Regulated MAP Kinases, Ginkgo biloba, Neoplasm Invasiveness, Neoplasm Metastasis, Butadienes, Matrix Metalloproteinase 2, Nitriles, Phosphorylation, Plant Extracts