Sun Yu, Lu Na, Ling Yun, Gao Ying, Chen Yan, Wang Ling, Hu Rong, Qi Qi, Liu Wei, Yang Yong, You Qidong, Guo Qinglong
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of China.
Eur J Pharmacol. 2009 Jan 28;603(1-3):22-8. doi: 10.1016/j.ejphar.2008.12.008. Epub 2008 Dec 10.
Our previous study revealed that oroxylin A, a naturally occurring monoflavonoid isolated from Scutellariae radix, could inhibit the proliferation of human hepatocellular carcinoma HepG2 cells through inducing the apoptosis in these cells. However, the molecular mechanism of its anticancer activity remains poorly understood and warrants further investigations. In this study, we examined the anti-invasive activities of oroxylin A in vitro. The results showed that oroxylin A suppressed MDA-MB-435 cell adhesion to the fibronectin-coated substrate in a concentration-dependent manner. It inhibited the wound healing migration of MDA-MB-435 cells and invasion of MDA-MB-435 cells through reconstituted extracellular matrix (matrigel). Zymography revealed that oroxylin A decreased the secretion of matrix metalloproteinases-2 (MMP-2) and metalloproteinases-9 (MMP-9). Oroxylin A also inhibited the expressions of MMP-2 and MMP-9 in MDA-MB-435 cells. Additionally, oroxylin A exerted an inhibitory effect on the phosphorylation of extracellular regulated proteinkinases1/2 (ERK1/2). Collectively, these data provided a molecular basis for the antiinvasive effects of oroxylin A. Taken together, these findings strongly suggest that oroxylin A had potential anti-metastatic effect in vitro and shed light on the investigation of oroxylin A on breast cancer metastasis in vivo.
我们之前的研究表明，从黄芩中分离出的天然单黄酮木犀草素A可通过诱导人肝癌HepG2细胞凋亡来抑制其增殖。然而，其抗癌活性的分子机制仍知之甚少，值得进一步研究。在本研究中，我们检测了木犀草素A的体外抗侵袭活性。结果表明，木犀草素A以浓度依赖的方式抑制MDA-MB-435细胞与纤连蛋白包被底物的黏附。它抑制MDA-MB-435细胞的伤口愈合迁移以及通过重组细胞外基质（基质胶）对MDA-MB-435细胞的侵袭。酶谱分析显示，木犀草素A减少了基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的分泌。木犀草素A还抑制MDA-MB-435细胞中MMP-2和MMP-9的表达。此外，木犀草素A对细胞外调节蛋白激酶1/2（ERK1/2）的磷酸化具有抑制作用。总的来说，这些数据为木犀草素A的抗侵袭作用提供了分子基础。综上所述，这些发现强烈表明木犀草素A在体外具有潜在的抗转移作用，并为木犀草素A对乳腺癌体内转移的研究提供了线索。
