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.