Wogonin suppresses melanoma cell B16-F10 invasion and migration by inhibiting Ras-medicated pathways.

Wogonin suppresses melanoma cell B16-F10 invasion and migration by inhibiting Ras-medicated pathways.
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DOI:
10.1371/journal.pone.0106458
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Lu N
Lu N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhao K;Wei L;Hui H;Dai Q;You QD;Guo QL;Lu N

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诊断为黑色素瘤的患者因早期区域浸润和远处转移而预后不良。汉黄芩素(5,7-dihydroxy-8-methoxyflavone,Wogonin)是从黄芪中提取的黄酮类化合物的活性成分之一。汉黄芩素具有抗白血病、胃肠道肿瘤和乳腺癌的作用。本研究以黑色素瘤细胞B16-F10为模型,进一步研究汉黄芩素的抗侵袭和抗迁移活性。汉黄芩素通过抑制基质金属蛋白酶2和Rac 1的表达,抑制细胞的迁移、粘附、侵袭和肌动蛋白重构。汉黄芩素在体内也能减少整个肺表面的肿瘤结节数量。进一步的机制研究表明,汉黄芩素对Ras介导的细胞外调节蛋白激酶和蛋白激酶B途径具有抑制作用。汉黄芩素还能抑制胰岛素样生长因子-1或肿瘤坏死因子-α诱导的细胞侵袭。因此,汉黄芩素抑制黑色素瘤细胞侵袭的机制可能得到阐明。
The patients diagnosed with melanoma have a bad prognosis for early regional invasion and distant metastases. Wogonin (5,7-dihydroxy-8-methoxyflavone) is one of the active components of flavonoids that extracts from Scutellariae radix. Several previous studies reported that wogonin possesses antitumor effect against leukemia, gastrointestinal cancer and breast cancer. In this study, we used melanoma cell B16-F10 to further investigate the anti-invasive and anti-migratory activity of wogonin. Our date showed that wogonin caused suppression of cell migration, adhesion, invasion and actin remodeling by inhibiting the expression of matrix metalloproteinase-2 and Rac1 in vitro. Wogonin also reduced the number of the tumor nodules on the whole surface of the lung in vivo. Furthermore, the examination of mechanism revealed that wogonin inhibited Extracellular Regulated protein Kinases and Protein Kinase B pathways, which are both medicated by Ras. Insulin-like growth factor-1-induced or tumor necrosis factor-α-induced invasion was also inhibited by wogonin. Therefore, the inhibitory mechanism of melanoma cell invasion by wogonin might be elucidated.
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