Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2
Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2
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DOI：
10.1016/j.taap.2005.11.010
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发表时间：
2006-07-01
影响因子：
3.8
通讯作者：
Chou, Fen-Pi
中科院分区：
文献类型：
--
作者：
Peng, Pei-Ling;Hsieh, Yih-Shou;Chou, Fen-Pi
小檗碱是一种从中草药中分离出来的化合物，具有抗癌、抗炎等药理作用。在这项研究中，我们观察到小檗碱在非细胞毒性浓度下对高度转移的A549细胞的运动和侵袭能力具有剂量和时间依赖性的抑制作用。在癌细胞的迁移和侵袭过程中，需要基质降解蛋白酶。明胶和酪蛋白酶谱分析显示，经不同浓度小檗碱处理的A549细胞ECM蛋白酶包括基质金属蛋白酶-2 （MMP2）和尿激酶-纤溶酶原激活物（u-PA）均降低。抑制作用可能是在转录水平上，因为转录水平的降低与蛋白质的减少相对应。此外，小檗碱还通过调节金属蛋白酶-2 （TIMP-2）组织抑制剂和尿激酶-纤溶酶原激活物抑制剂（PAI）发挥作用。该效应的上游介质涉及c-jun， c-fos和NF-kappa B，这可以通过降低这些蛋白的磷酸化来证明。这些发现提示，小檗碱在非小细胞肺癌细胞中具有抗转移作用，可能有助于临床治疗。(c) 2005爱思唯尔公司版权所有。
Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and antiinflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-kappa B, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment. (c) 2005 Elsevier Inc. All rights reserved.