川陳皮素透過PI3K/AKT/mTOR路徑誘發膀胱癌細胞凋亡及細胞轉移之研究

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题名:	川陳皮素透過PI3K/AKT/mTOR路徑誘發膀胱癌細胞凋亡及細胞轉移之研究
作者:	吳裕仁
贡献者:	健康暨護理學院
关键词:	Nobiletin bladder cancer cells apoptosis
日期:	2019-12
上传时间:	2020-12-07T07:56:51Z (UTC)
摘要:	Nobiletin (NOB) is a polymethoxylated flavonoid isolated from citrus fruit peel that has been shown to possess anti-tumor, antithrombotic, antifungal, anti-inflammatory and anti-atherosclerotic activities. The main purpose of this study was to explore the potential of using NOB to induce apoptosis in human bladder cancer cells and study the underlying mechanism. Using an MTT assay, agarose gel electrophoresis, a wound-healing assay, flow cytometry and western blot analysis, this study investigated the signaling pathways involved in NOB-induced apoptosis in BFTC human bladder cancer cells. Our results showed that NOB at concentrations of 60, 80 and 100 μM inhibited cell growth by 42, 62 and 80%, respectively. Cells treated with 60 μM NOB demonstrated increased DNA fragmentation, and flow cytometry analysis confirmed that the treatment caused late apoptotic cell death. Western blot analysis showed that mitochondrial dysfunction occurred in NOB-treated BFTC cells, leading to cytochrome C release into cytosol, activation of pro-apoptotic proteins (caspase-3, caspase-9, Bad and Bax), and inhibition of anti-apoptotic proteins (Mcl-1, Bcl-xl and Bcl-2). NOB-induced apoptosis was also mediated by regulating endoplasmic reticulum stress via the PERK/elF2α/ATF4/CHOP pathway, and downregulating the PI3K/AKT/mTOR pathway. Our results suggested that the cytotoxic and apoptotic effects of NOB on bladder cancer cells are associated with endoplasmic reticulum stress and mitochondrial dysfunction.
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