Sauchinone inhibits hypoxia-induced epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma cells through the Wnt/β-catenin pathway.

Abstract

The hypoxic microenvironment is commonly found in various solid tumors including pancreatic ductal adenocarcinoma (PDAC). Saururus chinensis is a medicinal Chinese herb widely used because of documented anti-inflammatory and anti-angiogenic properties. Sauchinone is special active lignin extracted from S. chinensis and its biological functions have been extensively explored. Recent studies have found that sauchinone could affect tumor initiation, metastasis and progression of some cancers. However, the specific role of sauchinone in PDAC remains to be elucidated. The main aim of this study was to elucidate the involvement of sauchinone in the progression of PDAC under the hypoxic condition. The human PDAC cell lines PANC-1 and BxPC-3 were exposed to hypoxia and various concentrations of sauchinone. The CCK-8 assay was performed to detect cytotoxic effects of sauchinone on PDAC cells. The levels of vascular endothelial growth factor, hypoxia-inducible factor-1α, E-cadherin, N-cadherin, Wnt3a and β-catenin were examined by the western blot analysis. Wound healing and transwell assays were used to assess cell migration and invasion. The results showed that the migratory and invasive abilities of PDAC cells were enhanced after exposure to hypoxia and the expression of epithelial-mesenchymal transition markers was also significantly regulated by hypoxia. All these effects induced under the hypoxic condition were terminated by sauchinone treatment. In addition, sauchinone suppressed hypoxia-induced activation of the Wnt/β-catenin signaling pathway. Our study provided important insight into understanding the mechanisms of the anti-cancer effect of sauchinone. Taken together, we suggested that sauchinone may be considered a new therapeutic agent for PDAC treatment.