Sauchinone inhibits hypoxia-induced invasion and epithelial–mesenchymal transition in osteosarcoma cells via inactivation of the sonic hedgehog pathway

Abstract

Hypoxia is a typical feature of solid tumors and is closely associated with tumor progression. Sauchinone, a biologically diastereomeric lignan, is isolated from the root of Saururus chinensis and has been widely used for the treatment of various diseases. Recently, sauchinone has been reported to play an anti-cancer role in cancer development under normoxia or hypoxia. However, the specific effects of sauchinone on osteosarcoma (OS) remain unclear. The aim of the present study was to investigate the role of sauchinone in OS progression under hypoxic conditions. The human OS cell lines U2OS and MG-63 were exposed to hypoxia followed by treatment with sauchinone. Cell viability was assessed by the CCK-8 assay. Cell migration and invasion were detected by transwell assays. The expression levels of VEGF, HIF-1α, E-cadherin and N-cadherin were examined by the western blot analysis. Our study showed that OS cell migration and invasion were significantly enhanced by hypoxia. Besides, hypoxic conditions resulted in a remarkable change in the expression of EMT markers. All these effects induced by hypoxia were abrogated by sauchinone treatment. Moreover, sauchinone inhibited hypoxia-induced activation of the sonic hedgehog (Shh) pathway. Additionally, the Shh agonist reversed the inhibitory effect of sauchinone on hypoxia-induced invasion and EMT of OS cells. In conclusion, these findings demonstrated that sauchinone inhibits hypoxia-induced invasion and EMT in OS cells via inactivation of the Shh pathway. We provided a novel insight for understanding the mechanisms underlying the anti-cancer effect of sauchinone and suggested sauchinone as a promising agent for OS treatment.