Meiho University Institutional Repository:Item 987654321/3576
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    题名: Sinulariolide Suppresses Cell Migration and Invasion by Inhibiting Matrix Metalloproteinase-2/-9 and Urokinase through the PI3K/AKT/mTOR Signaling Pathway in Human Bladder Cancer Cell
    作者: Cheng, Te-Chih
    Din, Zhong-Hao
    Su, Jui-Hsin
    Wu, Yu-Jen
    Liu, Chih-I
    贡献者: sinulariolide;human bladder cancer;migration;invasion;PI3K/AKT/mTOR
    关键词: sinulariolide;human bladder cancer;migration;invasion;PI3K/AKT/mTOR signaling pathway
    日期: 2018-09-03
    上传时间: 2018-09-04T06:46:20Z (UTC)
    摘要: 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.
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