Peng Pei-Ling, Hsieh Yih-Shou, Wang Chau-Jong, Hsu Jui-Ling, Chou Fen-Pi
Institute of Biochemistry and Biotechnology, College of Medicine, Chung Shan Medical University, No 110, section 2, Chien Kauo N. Road, Taichung 402, Taiwan, ROC.
Toxicol Appl Pharmacol. 2006 Jul 1;214(1):8-15. doi: 10.1016/j.taap.2005.11.010. Epub 2006 Jan 4.
Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation 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-kappaB, 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.
黄连素是从草药中分离出的一种化合物，据报道具有许多与抗癌和抗炎能力相关的药理作用。在本研究中，我们观察到黄连素在非细胞毒性浓度下对高转移性A549细胞的运动和侵袭能力具有剂量和时间依赖性抑制作用。在癌细胞迁移和侵袭过程中，需要基质降解蛋白酶。通过明胶和酪蛋白酶谱分析，用不同浓度黄连素处理的A549细胞显示出包括基质金属蛋白酶-2（MMP2）和尿激酶型纤溶酶原激活剂（u-PA）在内的细胞外基质蛋白酶减少。这种抑制作用可能在转录水平，因为转录本水平的降低与蛋白质水平相对应。此外，黄连素还通过调节金属蛋白酶组织抑制剂-2（TIMP-2）和尿激酶型纤溶酶原激活剂抑制剂（PAI）发挥作用。该作用的上游介质涉及c-jun、c-fos和核因子κB，这可通过蛋白质磷酸化减少得到证明。这些发现表明黄连素在非小细胞肺癌细胞中具有抗转移作用，因此可能有助于临床治疗。
