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Please use this identifier to cite or link to this item: http://ir.hwai.edu.tw:8080/ir/handle/310996100Q/1644

Title: Reversine抑制肺癌細胞的生長並誘導細胞凋亡及細胞自噬作用
Reversine inhibits cell growth and induces apoptosis and autophagy in lung cancer cells
Authors: 廖記德
Liao, Ji-Der
Keywords: 細胞凋亡
Lung cancer
Date: 2013
Issue Date: 2013-11-01 11:21:47 (UTC+8)
Abstract: Reversine ,2-(4-morpholinoanilino)-6-cyclohexylaminopurine 為小分子的普林合成類似物,曾被應用於幹細胞的研究上。過去有研究曾指出Reversine對於腫瘤具有抑制的效果,但它在肺癌的效果仍尚未明確。我們以Reversine處理肺癌細胞株A549、H23及H1299,並探討其相關機制路徑。首先,我們證實Reversine能抑制肺癌細胞的生長及聚落形成。進一步的研究顯示Reversine會誘導細胞週期停滯於G2/M期,並且產生細胞多倍體的現象。Reversine會降低肺癌細胞的Aurora-A及Aurora-B蛋白表現,並且降低下游p-Akt(Ser473)、p-GSK-3alpha(Ser21)及p-GSK-3beta(Ser9)的蛋白表現。 切割之caspase-3及PARP的出現證實Reversine可誘導肺癌細胞凋亡。LC3-II蛋白的增加顯示細胞自噬作用也參與其中。總結,Reversine可抑制肺癌細胞的生長及誘導細胞凋亡與細胞自噬作用,這樣的結果可以作為未來肺癌治療藥物開發上的一個新方向。
Reversine ,2-(4-morpholinoanilino)-6-cyclohexylaminopurine, a small synthetic purine analogue, has been used for stimulating stem cell dedifferentiation. It has been reported that reversine is effective in tumor suppression, but it’s effect in lung cancer cells remains unclear. We treated lung cancer cell lines A549, H23 and H1299 with reversine and disseted the related pathways. First, we demonstrated reversine inhibited cell growth and colony formation. Further results revealed reversine induced cell cycle arrested at G2/M phase and formed polyploidy. The expressions of Aurora-A, Aurora-B, p-Akt(Ser473), p-GSK-3alpha(Ser21) and p-GSK-3beta(Ser9) were down-regulated The presence of cleaved caspase-3 and PARP demonstrated reversine in reversine treated cells could induce apoptosis. That the increased LC3-II protein was present after reversine treatment implied that the autophagy is also involved. Taken together, reversine suppressed cell growth of lung cancer cells and induced apoptosis as well as autophagy, which may be an unique advantage for developing novel therapeutic agents for treatment of lung cancers in the future.
Appears in Collections:[醫學檢驗生物技術系碩士班] 博碩士論文

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