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.