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汉黄芩素通过抑制Ras介导的信号通路抑制黑色素瘤细胞B16-F10的侵袭和迁移。

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

作者信息

Zhao Kai, Wei Libin, Hui Hui, Dai Qinsheng, You Qi-Dong, Guo Qing-Long, Lu Na

机构信息

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing, People's Republic of China.

出版信息

PLoS One. 2014 Sep 9;9(9):e106458. doi: 10.1371/journal.pone.0106458. eCollection 2014.

Abstract

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.

摘要

被诊断为黑色素瘤的患者对于早期区域侵袭和远处转移预后不佳。汉黄芩素(5,7 - 二羟基 - 8 - 甲氧基黄酮)是从黄芩中提取的黄酮类活性成分之一。先前的多项研究报道,汉黄芩素对白血病、胃肠道癌和乳腺癌具有抗肿瘤作用。在本研究中,我们使用黑色素瘤细胞B16 - F10进一步研究汉黄芩素的抗侵袭和抗迁移活性。我们的数据表明,汉黄芩素在体外通过抑制基质金属蛋白酶 - 2和Rac1的表达来抑制细胞迁移、黏附、侵袭和肌动蛋白重塑。汉黄芩素在体内还减少了肺全表面的肿瘤结节数量。此外,机制研究表明,汉黄芩素抑制了均由Ras介导的细胞外调节蛋白激酶和蛋白激酶B途径。汉黄芩素还抑制了胰岛素样生长因子 - 1诱导的或肿瘤坏死因子 - α诱导的侵袭。因此,汉黄芩素对黑色素瘤细胞侵袭的抑制机制可能得以阐明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82fa/4159230/91cd2b4c203e/pone.0106458.g001.jpg

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