α-Solanine 抑制人類黑色素瘤細胞侵襲及爬行之研究

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Title:	α-Solanine 抑制人類黑色素瘤細胞侵襲及爬行之研究 The inhibitory effects of ?#8208;solanine on the invasion and migration in human melanoma cells
Authors:	張簡賜聰
Contributors:	嘉南藥理科技大學：生物科技系暨研究所陳品晟
Keywords:	侵襲爬行人類黑色素瘤細胞基質蛋白金屬酶茄科鹼 Invasion Migration human melanoma cell Matrix metalloproteinase (MMPs) α-Solanine
Date:	2009
Issue Date:	2011-10-27 14:43:03 (UTC+8)
Abstract:	α-Solanine 是由馬鈴薯芽眼中所萃取出來的天然固醇類生物鹼。近來有研究指出其具有抗癌能力，包括抑制腫瘤細胞增生及誘發細胞凋亡。可是，α-Solanine 對癌細胞轉移方面的研究尚不清楚，因此本論文目的在研究 α-Solanine 對人類黑色素瘤細胞A2058爬行及侵襲的抑制作用。我們發現高濃度的α-Solanine 會抑制細胞生長，所以測試低濃度α-Solanine 是否會抑制爬行和侵襲的能力。分別透過體外傷口癒合試驗及Boyden chamber侵襲試驗發現，細胞的爬行及侵襲能力均明顯受α-Solanine 抑制。利用gelatin zymography實驗也發現α-Solanine 降低基質金屬蛋白酶 (MMP-2/9) 的活性，另外運用西方墨點法，也發現α-Solanine 可抑制細胞內訊息傳遞因子包括JNK、ERK及P38等MAPK與PI3K、AKT的磷酸化作用。最後亦證實 α-Solanine 抑制轉錄因子NF-κB表現情形。綜合以上結果，推測α-Solanine 可能經由抑制 JNK/ERK/P38與PI3K/AKT等訊息傳遞路徑，降低了 MMP-2/9 的活性，進而抑制人類黑色素瘤細胞A2058的爬行及侵襲能力。 α-Solanine , isolated from Solanum tuberosum Linn., is a naturally occurring steroidal glycoalkaloid in potato sprouts and has been shown to inhibit tumor cells proliferation. However, the effect of α-Solanine on metastasis of cancer cell is still unclear. In the present study, we aimed to elucidate the potential of the glycoalkaloid on suppressing the migration and invasion in human melanoma cell A2058. α-Solanine could inhibit A2058 cells proliferation in a dose-dependent manner. To role out the cytotoxic effects, the nontoxic doses of α-Solanine were utilized to examine its anti-migratory and anti-invasive activitie. We demonstrated that the cells migration and invasion were suppressed significantly by in vitro wound healing assay and Boyden chamber invasion assay, respectively. α-Solanine also suppressed the activity of matrix metalloproteinase-2/9, which are involved in cell migration and invasion. In addition, α-Solanine decreased the phosphorylation of JNK、ERK、P38 and PI3K /AKT in A2058 cells. In addition, α-Solanine increased the cytoplasmic level of IκB and decreased the nuclear level of NF-κB. Taken together, the results suggested that α-Solanine inhibited human melanoma cells migration and invasion through the reduction of MMP-2/9 activities by suppressing MAPK and PI3K/AKT/ NF-κB pathways.
Relation:	校內校外均不公開，學年度：97，79 頁
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Dissertations and Theses

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