Division of Nephrology, Department of Medicine, Taoyuan General Hospital, Taoyuan 330, Taiwan.
Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
Int J Mol Sci. 2018 May 31;19(6):1630. doi: 10.3390/ijms19061630.
The roles of Matrix MetalloProteinases (MMPs), such as MMP-9, in tumor metastasis are well studied, and this in turns stimulates the development of MMP inhibitors as antitumor agents. Previously, accumulation was observed in the metastatic nodules of the lungs after systemic administration. significantly enhanced the survival of the pulmonary metastatic tumor-bearing mice. Based on our previous observation, we hypothesized that could affect metastasis-related protein expression. The treatment of clearly reduced the expression of MMP-9. Meanwhile, the MMP-9 related signaling pathways, including Phosph-Protein Kinase B (P-AKT) and Phosph-mammalian Targets Of Rapamycin (P-mTOR) were decreased after a treatment. The inhibited tumor cell migration by wound-healing and Transwell assay. The anti-metastatic effects of were evaluated in mice bearing experimental metastasis tumor models. Consequently, inhibited the expression of MMP-9 by reducing the AKT/mTOR pathway and metastatic nodules in vivo.
基质金属蛋白酶（MMPs）的作用，如 MMP-9，在肿瘤转移中得到了很好的研究，这反过来又刺激了 MMP 抑制剂作为抗肿瘤药物的发展。以前，在全身给药后，在肺部转移结节中观察到了 的积累。 显著提高了肺转移荷瘤小鼠的存活率。基于我们之前的观察，我们假设 可能会影响与转移相关的蛋白表达。 的治疗明显降低了 MMP-9 的表达。同时，MMP-9 相关信号通路，包括磷酸蛋白激酶 B（P-AKT）和磷酸雷帕霉素靶蛋白（P-mTOR）在 处理后减少。 通过划痕愈合和 Transwell 分析抑制肿瘤细胞迁移。在携带实验性转移肿瘤模型的小鼠中评估了 的抗转移作用。结果， 通过降低 AKT/mTOR 通路和体内转移结节来抑制 MMP-9 的表达。
