姜的活性成分 6-姜酚通过阻断核因子-κB 的激活减少基质金属蛋白酶-9 的表达，从而抑制乳腺癌细胞的侵袭。
6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation.
机构信息
Department of Pharmacy, National University of Singapore, Singapore, Singapore.
出版信息
Br J Pharmacol. 2010 Dec;161(8):1763-77. doi: 10.1111/j.1476-5381.2010.00991.x.
BACKGROUND AND PURPOSE
Shogaols are reported to possess anti-inflammatory and anticancer activities. However, the antimetastatic potential of shogaols remains unexplored. This study was performed to assess the effects of shogaols against breast cancer cell invasion and to investigate the underlying mechanisms.
EXPERIMENTAL APPROACH
The anti-invasive effect of a series of shogaols was initially evaluated on MDA-MB-231 breast cancer cells using the matrigel invasion assay. The suppressive effects of 6-shogaol on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 (MMP-9) gelatinolytic activity and nuclear factor-κB (NF-κB) activation were further determined.
KEY RESULTS
Shogaols (6-, 8- and 10-shogaol) inhibited PMA-stimulated MDA-MB-231 cell invasion with an accompanying decrease in MMP-9 secretion. 6-Shogaol was identified to display the greatest anti-invasive effect in association with a dose-dependent reduction in MMP-9 gene activation, protein expression and secretion. The NF-κB transcriptional activity was decreased by 6-shogaol; an effect mediated by inhibition of IκB phosphorylation and degradation that subsequently led to suppression of NF-κB p65 phosphorylation and nuclear translocation. In addition, 6-shogaol was found to inhibit JNK activation with no resulting reduction in activator protein-1 transcriptional activity. By using specific inhibitors, it was demonstrated that ERK and NF-κB signalling, but not JNK and p38 signalling, were involved in PMA-stimulated MMP-9 activation.
CONCLUSIONS AND IMPLICATIONS
6-Shogaol is a potent inhibitor of MDA-MB-231 cell invasion, and the molecular mechanism involves at least in part the down-regulation of MMP-9 transcription by targeting the NF-κB activation cascade. This class of naturally occurring small molecules thus have potential for clinical use as antimetastatic treatments.
背景与目的
姜烯酚具有抗炎和抗癌活性。然而，姜烯酚的抗转移潜力尚未得到探索。本研究旨在评估姜烯酚对乳腺癌细胞侵袭的影响，并探讨其潜在机制。
实验方法
首先使用基质胶侵袭实验评估一系列姜烯酚对 MDA-MB-231 乳腺癌细胞的抗侵袭作用。进一步测定 6-姜烯酚对佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）诱导的基质金属蛋白酶-9（MMP-9）明胶酶活性和核因子-κB（NF-κB）激活的抑制作用。
主要结果
姜烯酚（6-、8-和 10-姜烯酚）抑制 PMA 刺激的 MDA-MB-231 细胞侵袭，同时 MMP-9 分泌减少。6-姜烯酚显示出最大的抗侵袭作用，同时 MMP-9 基因激活、蛋白表达和分泌呈剂量依赖性降低。6-姜烯酚降低 NF-κB 转录活性；这种作用是通过抑制 IκB 磷酸化和降解介导的，随后导致 NF-κB p65 磷酸化和核转位抑制。此外，发现 6-姜烯酚抑制 JNK 激活，但不降低激活蛋白-1 转录活性。通过使用特异性抑制剂，表明 ERK 和 NF-κB 信号通路，但不包括 JNK 和 p38 信号通路，参与 PMA 刺激的 MMP-9 激活。
结论和意义
6-姜烯酚是 MDA-MB-231 细胞侵袭的有效抑制剂，其分子机制至少部分涉及通过靶向 NF-κB 激活级联下调 MMP-9 转录。因此，这类天然存在的小分子具有作为抗转移治疗的临床应用潜力。
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