Inhibitory Effects of Ethyl Pyruvate on Invasion and Metastasis of Human Gastric Cancer SGC-7901 Cells via Downregulation of Akt Pathway

Objective To explore the effects and molecular mechanisms of ethyl pyruvate (EP) on invasion and metastasis of human gastric cancer SGC-7901 cells. Methods MTT assay was used to evaluate IC50 of EP on human gastric cancer SGC-7901 cell line.After different concentrations of EP (0,10 mmol/L,20 mmol/L and 40mmol/L) were added into SGC-7901 cells,the expression levels of protein kinase B (Akt) and phosphorylated Akt (p-Akt) mRNA were identified by real-time PCR,and the expression levels of Akt,p-Akt,matrix metalloproteinase-2 (MMP-2) and MMP-9 protein were detected by Western blot.The invasive and metastatic activities of gastric cancer cells were evaluated by wound -healing and Transwell assay.SGC-7901 xenograft tumor model was established,and the protein expression of Akt,p -Akt,MMP-2 and MMP-9 was further validated by immunohistochemical analysis. Results The IC50 of EP on human gastric cancer SGC-7901 cells was about 36.73mmol/L.EP administration inhibited Akt mRNA expression,and downregulated Akt,p-Akt,MMP-2 and MMP-9 protein expression.Wound-healing assay indicated that the migration and exercise capability of SGC-7901 cells was reduced obviously;Transwell assay showed,in comparison with the control group (93.33±4.16),the number of invasive and metastatic cells infiltrated the matrigel in EP 10 mmol/L group(75.34±4.73),EP 20 mmol/L group (61.34±3.06) and EP 40 mmol/L group (39.00±3.00) was respectively decreased (each P<0.001).Immunohistochemical analysis further confirmed the expression levels of Akt,p-Akt,MMP-2 and MMP-9 protein shown by Western blot. Conclusion EP administration can inhibit the invasion and metastasis of human gastric cancer SGC-7901 cells via downregulation of Akt pathway,and it may play a crucial role in cancer therapy.