Korean Red Ginseng extract reduces hypoxia-induced epithelial-mesenchymal transition by repressing NF-κB and ERK1/2 pathways in colon cancer

摘要

Background: The incidence of colorectal cancer (CRC) is increasing, with metastasis of newly diagnosedCRC reported in a large proportion of patients. However, the effect of Korean Red Ginseng extracts (KRGE)on epithelial to mesenchymal transition (EMT) in CRC is unknown. Therefore, we examined the mechanismsby which KRGE regulates EMT of CRC in hypoxic conditions.Methods: Human CRC cell lines HT29 and HCT116 were incubated under hypoxic (1% oxygen) andnormoxic (21% oxygen) conditions. Western blot analysis and real-time PCR were used to evaluate theexpression of EMT markers in the presence of KRGE. Furthermore, we performed scratched woundhealing, transwell migration, and invasion assays to monitor whether KRGE affects migratory andinvasive abilities of CRC cells under hypoxic conditions.Results: KRGE-treated HT29 and HCT116 cells displayed attenuated vascular endothelial growth factor(VEGF) mRNA levels and hypoxia-inducible factor-1a (HIF-1a) protein expression under hypoxic conditions.KRGE repressed Snail, Slug, and Twist mRNA expression and integrin aVb6 protein levels.Furthermore, hypoxia-repressed E-cadherin was restored in KRGE-treated cells; KRGE blocked the invasionand migration of colon cancer cells by repressing NF-kB and ERK1/2 pathways in hypoxia.Conclusions: KRGE inhibits hypoxia-induced EMT by repressing NF-kB and ERK1/2 pathways in coloncancer cells.