Plumbagin is a natural naphthoquinone constituent isolated from the roots of medicinal plant Plumbago zeylanica L., and has demonstrated anti-proliferative and anti-invasion activities in various cancer cells. However, its effect on the migration and invasion of glioma cells has not been elucidated. Therefore, human glioma U87 and U251 cells were treated with plumbagin at 1.0 and 2.0 μM for 24 h, and cell migration and invasion were assessed with scratch wound healing and invasion assays. The results showed that plumbagin significantly inhibited the migration and invasion of U87 and U251 cells, suppressed the activity and expression of MMP-2/-9, and inhibited the nuclear translocation of transcription factors Sp1 in the U87 and U251 cells. Moreover, plumbagin reduced the level of p-PI3K and p-Akt in these cells. The combined treatment with plumbagin and PI3K/Akt agonist insulin-like growth factor-1 (IGF-1) reversed plumbagin-mediated inhibitory effects on MMP-2/-9 expression, cell migration and invasion. These findings suggest that the plumbagin-induced inhibition of glioma cell migration and invasion is closely associated with the downregulation of MMP-2/-9 expression and activity, and suppression of PI3K/Akt signaling pathway activation. Thus, plumbagin might be a potential anti-invasive agent in the treatment of glioma.
Keywords: Glioma; Invasion; Matrix metalloproteinase; Migration; Plumbagin.
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