Abstract: Sinulariolide is a natural product extracted from the cultured-type soft coral Sinularia
flexibilis, and possesses bioactivity against the movement of several types of cancer cells.
However, the molecular pathway behind its effects on human bladder cancer remain poorly
understood. Using a human bladder cancer cell line as an in vitro model, this study investigated
the underlying mechanism of sinulariolide against cell migration/invasion in TSGH-8301 cells.
We found that sinulariolide inhibited TSGH-8301 cell migration/invasion, and the effect was
concentration-dependent. Furthermore, the protein expressions of matrix metalloproteinases (MMPs)
MMP-2 and MMP-9, as well as urokinase, were significantly decreased after 24-h sinulariolide
treatment. Meanwhile, the increased expression of tissue inhibitors of metalloproteinases (TIMPs)
TIMP-1 and TIMP-2 were in parallel with an increased concentration of sinulariolide. Finally, the
expressions of several key phosphorylated proteins in the mTOR signaling pathway were also
downregulated by sinulariolide treatment. Our results demonstrated that sinulariolide has significant
effects against TSGH-8301 cell migration/invasion, and its effects were associated with decreased
levels of MMP-2/-9 and urokinase expression, as well as increased TIMP-1/TIMP-2 expression.
The inhibitory effects were mediated by reducing phosphorylation proteins of the PI3K, AKT, and
mTOR signaling pathway. The findings suggested that sinulariolide is a good candidate for advanced
investigation with the aim of developing a new drug for the treatment of human bladder cancer.
