Abstract
The peritoneal metastasis-associated phosphatase of regenerating liver-3 (PRL-3) is upregulated in gastric cancer. The phosphatidylinositol 3-kinase (PI3K)/RAC serine/threonine-protein kinase (AKT) signaling pathway acts downstream of PRL-3 in gastric cancer. However, the exact PRL-3 signaling mechanisms are poorly understood. The present study investigated whether PRL-3 facilitates the peritoneal metastasis of gastric cancer via the PI3K/AKT pathway in vivo and in vitro. Nude mouse models of peritoneal metastasis were established using SGC7901/PRL-3 cell lines. The results confirmed that the invasion and migration abilities of SGC7901/PRL-3 cells were significantly increased in these models. Furthermore, western blotting demonstrated that the expression of p-AKT, matrix metallopeptidase-2 (MMP-2) and -9 proteins increased in SGC7901/PRL-3 cells. These effects were suppressed in SGC7901 cell lines when PI3K was inhibited by LY294002. Furthermore, tumors derived from the peritoneal injection of SGC7901/PRL-3 cells were significantly smaller when the cells were grown in the presence of LY249002, compared with cells grown in its absence. These results indicated that targeted inhibition of the PI3K/AKT signaling pathway decreased the effects of PRL-3 on metastasis in vivo. Collectively, the results of the present study indicated that PRL-3 acts via the PI3K/AKT pathway to promote peritoneal metastasis and invasion of gastric cancer cells in vitro and in vivo.