青藤鹼抑制人類肺腺癌細胞轉移之研究

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Title:	青藤鹼抑制人類肺腺癌細胞轉移之研究 Study the effect of sinomenine on inhibiting cell metastasis in human lung cancer cells 青藤鹼是從防己科落葉纏繞藤本植物青藤及毛青藤的乾燥藤莖中提取的一種生物鹼。近期研究發現,青藤鹼可以抑制乳癌細胞及大腸癌細胞的細胞增殖、爬行與侵入作用,並誘導細胞凋亡。本研究以體外試驗分析青藤鹼抑制人類肺腺癌細胞 A549 的侵入作用與其作用機轉。實驗結果顯示,青藤鹼會呈現劑量依賴性的方式去抑制 A549 細胞存活率。用低毒性劑量的青藤鹼處理細胞後,細胞侵入能力明顯受到抑制。青藤鹼顯著提升上皮細胞標記 E-cadherin 的 mRNA 表達,並降低間質細胞標記 vimentin 的mRNA 表達,顯示青藤鹼具有抑制上皮-間質細胞轉換的作用。青藤鹼也提升 RECK (reversion-inducing cysteine-rich protein with kazal motife) 及組織蛋白?抑制劑 (Tissue inhibit of metalloproteinases) TIMP-1/-2 的 mRNA 表達。此外,青藤鹼調降致癌微型核醣核酸 microRNA-21 (miR-21) 的表現量,其已知會標靶 RECK。利用 miR-21 抑制劑來調降細胞內的 miR-21 表現,發現可增加 RECK 的 mRNA 表現量,並降低細胞侵入能力。綜合以上研究結果,顯示青藤鹼可能經由調降 miR-21 的表達而提升 RECK 的mRNA 表達,並抑制細胞侵入作用。本研究顯示,青藤鹼可能具有成為抗腫瘤轉移治療藥物的潛力。關鍵字:青藤鹼;microRNA-21 (miR-21);RECK;腫瘤侵襲;肺癌。 Sinomenine is an alkaloid extracted from the root of the climbing plantSinomenine acutum. Recent studies found that sinomenine can inhibitproliferation, migration, invasion, and inducing apoptosis in breast and colorectal cancer cell. This study is aimed to investigate the effect and mechanism of sinomenine on inhibiting invasion on human lung adenocarcinoma cell line A549 in vitro. Results demonstrate that viability of A549 cell was inhibited by sinomenine in a dose-dependent manner. When treated with sub-toxic dose of sinomenine, cell invasion is markedly suppressed. Sinomenine also significantly elevates epithelial marker E-cadherin expression, while it concomitantly decreases mesenchymal marker vinmetin expression, suggesting it suppresses epithelial- mesenchymal transition (EMT). Sinomenine increase the mRNA level of reversion-inducing cysteine-rich protein with kazal motifs (RECK), as well as tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Moreover,sinomenine downregulates oncogenic microRNA-21 (miR-21), which has been known to target RECK. Downregulation of miR-21 by miR-21 inhibitor increase RECK expression and decreases cell invasion, suggesting that downregulation of miR-21 by sinomenine may contribute to elevate RECK expression and subsequently inhibiting cell invasion. Taken together, the results reveal inhibition of A549 cell invasion by sinomenine may be, at least in part, through downregulating expression of miR-21. These findings demonstrate an attractive therapeutic potential for expression of in lung cancer anti-metastasis therapy.Key words:sinomenine;microRNA-21 (miR-21);RECK;invasion;Lung cancer.
Authors:	廖苡晴
Contributors:	生物科技系陳品晟
Keywords:	青藤鹼 Sinomenine
Date:	2020
Issue Date:	2022-10-21 10:26:50 (UTC+8)
Relation:	學年度：108， 69頁
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Dissertations and Theses

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