Repression of matrix metalloproteinase gene expression by ginsenoside Rh2 in human astroglioma cells
Repression of matrix metalloproteinase gene expression by ginsenoside Rh2 in human astroglioma cells
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DOI：
10.1016/j.bcp.2007.08.015
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发表时间：
2007-12-03
影响因子：
5.8
通讯作者：
Kim, Hee-Sun
中科院分区：
文献类型：
--
作者：
Kim, So-Young;Kim, Dong-Hyun;Kim, Hee-Sun
基质金属蛋白酶（Matrix metalloproteinases, MMPs）通过降解细胞外基质在胶质瘤浸润、促进细胞迁移和肿瘤侵袭中发挥重要作用。因此，抑制MMPs被认为是一种很有前景的脑肿瘤治疗策略。本研究探讨了人参皂苷Rh2对人星形胶质瘤细胞中MMPs表达的影响。Rh2可抑制pma诱导的MMP-1、-3、-9和-14 mRNA的表达，提示Rh2对MMPs具有广谱抑制作用。由于MMP-9在胶质瘤侵袭中起主要作用，因此进一步研究了MMP-9抑制的分子机制。结果发现，Rh2可抑制PMA诱导的人星形胶质瘤细胞中MMP-9的分泌和蛋白表达。rh2介导的对MMP-9基因表达的抑制似乎是通过NF-kappa B和AP-1发生的，因为它们的DNA结合和转录活性被rh2抑制。此外，Rh2显著抑制pma介导的p38 MAPK、ERK和JNK的激活，而p38 MAPK、ERK和JNK是NF-kappa B和AP-1的上游调节剂。最后，Rh2抑制了胶质瘤细胞的体外侵袭性，这可能与Rh2对MMPs的广谱抑制有关。总之，Rh2对MMP表达的强烈抑制可能为脑肿瘤的治疗提供了一种潜在的治疗方式。(c) 2007爱思唯尔公司版权所有。
Matrix metalloproteinases (MMPs) play an important role in glioma infiltration, facilitating cell migration and tumor invasion through their ability to degrade the extracellular matrix. Therefore, the inhibition of MMPs has been suggested to be a promising therapeutic strategy for brain tumors. This study examined the effect of ginsenoside Rh2 on the expression of MMPs in human astroglioma cells. Rh2 inhibited the PMA-induced mRNA expression of MMP-1, -3, -9, and -14, suggesting that Rh2 has a broad-spectrum inhibitory effect on MMPs. The molecular mechanism underlying MMP-9 inhibition was further investigated because MMP-9 plays a major role in the invasiveness of glioma. It was found that Rh2 inhibited the secretion and protein expression of MMP-9 induced by PMA in human astroglioma cells. The Rh2-mediated inhibition of MMP-9 gene expression appears to occur through NF-kappa B and AP-1 because their DNA binding and transcriptional activities were suppressed by the agent. Furthermore, Rh2 significantly repressed the PMA-mediated activation of p38 MAPK, ERK and JNK, which are upstream modulators of NF-kappa B and AP-1. Finally, Rh2 inhibited the in vitro invasiveness of glioma cells, which might be attributed to the broad-spectrum inhibition of MMPs by Rh2. Overall, the strong inhibition of MMP expression by Rh2 might provide a potential therapeutic modality for brain tumors. (c) 2007 Elsevier Inc. All rights reserved.