α‐Chaconine 抑制內皮細胞的爬行與侵入之研究

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Title:	α‐Chaconine 抑制內皮細胞的爬行與侵入之研究 α-Chaconine inhibits endothelial cell migration and invasion
Authors:	陳沛嫺
Contributors:	嘉南藥理科技大學：生物科技系暨研究所陳品晟
Keywords:	侵入牛動脈內皮細胞基質蛋白金屬酶爬行 JNK NF-κB 血管新生 ERK α-chaconine bovine aortic endothelial cells（BAECs） invasion matrix metalloproteinase（MMP） extracellular signal regulating kinase（ERK） α-chaconine angiogenesis migration c-Jun N-terminal kinase（JNK） nuclear factor kappa B（NF-κB）
Date:	2009
Issue Date:	2011-10-27 14:43:06 (UTC+8)
Abstract:	α-Chaconine是由茄科馬鈴薯芽眼中所萃取出來的天然固醇類生物鹼。有研究指出其具抗癌活性，包括能抑制腫瘤細胞增生及誘發細胞凋亡。然而，α-chaconine在腫瘤的血管新生方面的研究尚未明瞭。本研究發現α-chaconine能抑制牛動脈內皮細胞（BAECs）的增生及管柱形成現象，並具有劑量依循性模式的相關性。當以非毒性劑量的α-chaconine處理細胞，分別透過體外傷口癒合試驗及boyden chamber爬行與侵入試驗發現到，細胞的爬行及侵入能力均明顯受抑制。α-Chaconine能抑制內皮細胞的貼附能力，同樣也降低了基質金屬蛋白酶-2（MMP-2）的活性，而MMP-2牽涉到細胞爬行及侵入能力。同時，α-chaconine能降低BAECs的JNK、PI3K及Akt三種蛋白質的磷酸化現象，卻不影響ERK、p38蛋白質的磷酸化現象。此外，α-chaconine能使核外IκB-α的表現增加，並且減少核內NF-κB的表現，因而推測α-chaconine能降低NF-κB的活性。因此，由上述結果我們發現α-chaconine可能經由抑制MAPK及PI3K/Akt/NF-κB這些路徑，降低MMP-2的活性，進而抑制內皮細胞的爬行及侵入。這些結果顯示，α-chaconine在未來抗血管新生的治療上，會是個新的潛力軍。 α-Chaconine, isolated from Solanum tuberosum Linn., is a naturally occurring steroidal glycoalkaloid in potato sprouts. Some reports demonstrated that α-chaconine had various anticarcinogenic properties, such as inhibiting tumor cells proliferation and inducing apoptosis. However, the effect of α-chaconine on tumor angiogenesis remains unclear. In the present study, we showed that α-chaconine inhibited proliferation and tube formation of bovine aortic endothelial cells (BAECs) in a dose-dependent manner. When treated with non-toxic doses of α-chaconine, cells migration and invasion were suppressed significantly by in vitro wound healing assay and Boyden chamber invasion assay, respectively. The adhesion of BAECs was suppressed by α-chaconine. α-Chaconine also reduced the activity of matrix metalloproteinase-2 (MMP-2), which is involved in cell migration and invasion. We also showed that α-chaconine could decrease the phosphorylation of c-Jun N-terminal kinase (JNK) and Phosphatidylinositol 3-kinase (PI3K)/ Akt in BAECs, while it did not affect the phosphorylation of extracellular signal regulating kinase (ERK) and p38 in BAECs. In addition, α-chaconine significantly decreased the nuclear protein level of nuclear factor kappa B (NF-κB) and increased the cytosolic protein level of IκB-α, suggesting that α-chaconine reduced the activity of NF-κB. Taken together, the results suggested that α-chaconine inhibited BAECs migration and invasion by reducing MMP-2 activity through the suppression of MAPK and PI3K/Akt/NF-κB signaling pathways. These findings reveal a new therapeutic potential for α-chaconine on anti-angiogenic therapy.
Relation:	校內校外均不公開，學年度：97， 77 頁
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Dissertations and Theses

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