Resveratrol inhibits the invasion and metastasis of colon cancer through reversal of epithelial- mesenchymal transition via the AKT/GSK-3β/Snail signaling pathway

Abstract

The identification of safe and effective drugs that inhibit tumor invasion and metastasis is required to improve the clinical outcome of patients with colon cancer. The present study aimed to investigate the inhibitory effects and possible mechanisms of action of resveratrol against the invasion and metastasis of colon cancer. AKT1-knockdown SW480 and SW620 colon cancer cells were used to detect the effects of resveratrol on cell invasion and metastasis, as well as changes in the expression of epithelial-mesenchymal transition (EMT) markers and serine/threonine kinase (AKT)/glycogen synthase kinase (GSK)-3β/Snail signaling pathway-related molecules in vitro. Furthermore, nude mice were inoculated with SW480 cells in the tail vein to establish an in vivo lung metastasis model of colon cancer, to investigate the effects of resveratrol on lung metastasis in colon cancer. The results revealed that resveratrol treatment and AKT1 knockdown significantly inhibited cell migration and invasion in colon cancer, and markedly increased E-cadherin expression and decreased that of N-cadherin, phospho (p)-AKT1, p-GSK-3β, and Snail in colon cancer both in vitro and in vivo. Furthermore, the effects of resveratrol were significantly weaker in the AKT1-knockdown cells. In conclusion, resveratrol may suppress the invasion and metastasis of colon cancer through reversal of EMT via the AKT/GSK-3β/Snail signaling pathway. AKT1 may therefore be a key regulator of EMT in colon cancer cells and a potential therapeutic target for this disease.