首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Protopanaxatriol ginsenoside Rh1 inhibits the expression of matrix metalloproteinases and the in vitro invasion/migration of human astroglioma cells
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Protopanaxatriol ginsenoside Rh1 inhibits the expression of matrix metalloproteinases and the in vitro invasion/migration of human astroglioma cells

机译:人参皂甙Rtop1抑制基质金属蛋白酶的表达以及人星形胶质瘤细胞的体外侵袭/迁移

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摘要

Malignant gliomas are the most common and fatal brain tumors in adults. In particular, the strong invasiveness of glioma cells into the normal brain tissue makes eradication of glioma very difficult. Matrix metalloproteinases (MMPs) play a pivotal role in glioma invasion, and thus controlling MMP expression has been suggested as an important therapeutic target for brain tumors. In the present study, we investigated the effect of protopanaxatriol ginsenoside Rh1 on MMP expressions in human astroglioma U87MG and U373MG cells. RT-PCR analysis showed that Rh1 inhibits the mRNA expressions of MMP-1, -3, and -9 in PMA-stimulated U87MG and U373MG cells. Rh1 also suppressed the promoter activities of MMP-1, -3 and -9. The ELISA, Western blot, and zymographic analyses revealed that Rh1 inhibits the protein expression and/or enzymatic activity of MMP-1, -3 and -9. In accordance with the strong inhibitory effects of Rh1 on MMPs, Rh1 efficiently inhibited the invasion and migration of U87MG and U373MG glioma cells as demonstrated by Matrigel invasion assay and wound healing assay. Further mechanistic studies revealed that Rh1 inhibits MAPK and PI3K/Akt signaling pathways and downstream transcription factors such as NF-κB and AP-1, which play an important role in MMP gene expressions. The data collectively suggest that ginsenoside Rh1 may have a therapeutic potential for malignant gliomas.
机译:恶性神经胶质瘤是成人中最常见和致命的脑肿瘤。特别地,神经胶质瘤细胞对正常脑组织的强烈侵袭使得根除神经胶质瘤非常困难。基质金属蛋白酶(MMPs)在神经胶质瘤的侵袭中起着关键作用,因此控制MMP的表达被认为是脑肿瘤的重要治疗靶点。在本研究中,我们调查了人参神经胶质瘤U87MG和U373MG细胞中MMP的表达及其对人参原三醇人参皂甙Rh1的影响。 RT-PCR分析表明,Rh1抑制PMA刺激的U87MG和U373MG细胞中MMP-1,-3和-9的mRNA表达。 Rh1还抑制MMP-1,-3和-9的启动子活性。 ELISA,蛋白质印迹和酶谱分析表明,Rh1抑制MMP-1,-3和-9的蛋白表达和/或酶活性。根据Rh1对MMPs的强抑制作用,Rh1有效抑制了U87MG和U373MG胶质瘤细胞的侵袭和迁移,如Matrigel侵袭试验和伤口愈合试验所示。进一步的机理研究表明,Rh1抑制MAPK和PI3K / Akt信号通路以及下游转录因子,例如NF-κB和AP-1,它们在MMP基因表达中起重要作用。这些数据共同表明人参皂甙Rh1对恶性神经胶质瘤可能具有治疗潜力。

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