Herbal prescription, Danggui-Sayuk-Ga-Osuyu-Senggang-Tang, inhibits TNF--induced epithelial-mesenchymal transition in HCT116 colorectal cancer cells

Abstract

Tumor necrosis factor--mediated (TNF-) epithelial-mesenchymal transition (EMT) is associated with distant metastasis in patients with colorectal cancer with poor prognosis. Although traditional herbal medicines have long been used to treat colorectal cancer, the incidence and mortality in patients with colorectal cancer has continued to increase. Danggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST) has long been used for treatment of chills, while few studies have reported its anticancer effect. This study aimed to demonstrate the inhibitory effect of DSGOST on TNF--mediated invasion and migration of colorectal cancer HCT116 cell lines. MTT was used to measure cell viability. Wound healing and Transwell invasion assay were used to detect migration and invasion of cells, respectively. The intracellular localization of proteins of interest was assessed by immunocytochemistry. Western blotting was performed to determine the expression level of various proteins. A non-toxic dose of DSGOST (50 mu g/ml) on HCT116 cells was determined by MTT assay. Furthermore, DSGOST prevented the TNF--induced invasive phenotype in HCT116 cells. DSGOST inhibition of the invasive phenotype was also associated with increased expression of EMT markers. Furthermore, DSGOST treatment blocked TNF--induced migration and invasion of HCT116 cells. In addition, DSGOST treatment inhibited TNF--mediated nuclear translocation of Snail. DSGOST treatment also downregulated TNF--induced phosphorylation of AKT and glycogen synthase kinase-3. Therefore, the findings of the current study suggest that DSGOST exhibits anti-migration and anti-invasion effects in TNF--treated HCT116 human colorectal cells.