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姜黄素通过抑制 MMP-2、MMP-9、FAK、RhoA 和 Rock-1 基因的表达来阻止鼠-大鼠杂交视网膜神经节细胞(N18)的迁移和侵袭。

Curcumin blocks migration and invasion of mouse-rat hybrid retina ganglion cells (N18) through the inhibition of MMP-2, -9, FAK, Rho A and Rock-1 gene expression.

机构信息

Department of Ophthalmology, China Medical University Hospital, Taichung 404, Taiwan.

出版信息

Oncol Rep. 2010 Mar;23(3):665-70.

Abstract

Cancer metastasis involves multiple processes which may complicate clinical management and even lead to death. Matrix metalloproteinases (MMPs) play an important role in cancer cell invasion, metastasis and angiogenesis, depending on whether agents can inhibit MMPs which could lead to inhibition of the migration and invasion of cancer cells. Curcumin, the active constituent of the dietary spice turmeric, has potential for the prevention and therapy of cancer. However, there is no study to address the effects of curcumin on migration and invasion of mouse-rat hybrid retina ganglion cells (N18). This is the first study to explore the anti-migration and -invasion of curcumin in mouse-rat hybrid retina ganglion cells (N18) in vitro. Curcumin exerted a dose- and time-dependent inhibitory effect on the invasion and migration of N18 cells in vitro. Results from Western blotting showed that curcumin inhibited the protein levels of PKC, FAK, NF-kappaB p65 and Rho A leading to the inhibition of ERK1/2, MKK7, COX-2 and ROCK1, respectively, finally causing the inhibition of MMP-2 and -9 for the inhibition of migration and invasion of N18 cells. Moreover, this action was involved in the inhibition of gene expression of MMP-2 and -7, FAK, ROCK1 and Rho A. Overall, the above data show that the anticancer effect of curcumin also exists for the inhibition of migration and invasion in N18 cells, and that curcumin may be a powerful candidate for developing preventive agents for cancer metastasis.

摘要

癌症转移涉及多个过程,这可能会使临床管理变得复杂,甚至导致死亡。基质金属蛋白酶(MMPs)在癌细胞的侵袭、转移和血管生成中发挥重要作用,这取决于是否有药物可以抑制 MMPs,从而抑制癌细胞的迁移和侵袭。姜黄素是食用香料姜黄的活性成分,具有预防和治疗癌症的潜力。然而,目前还没有研究探讨姜黄素对鼠-大鼠杂交视网膜神经节细胞(N18)迁移和侵袭的影响。这是首次研究姜黄素对体外鼠-大鼠杂交视网膜神经节细胞(N18)迁移和侵袭的抑制作用。姜黄素对 N18 细胞的体外侵袭和迁移具有剂量和时间依赖性的抑制作用。Western blot 结果表明,姜黄素抑制 PKC、FAK、NF-κB p65 和 Rho A 的蛋白水平,分别导致 ERK1/2、MKK7、COX-2 和 ROCK1 的抑制,最终导致 MMP-2 和 -9 的抑制,从而抑制 N18 细胞的迁移和侵袭。此外,这种作用涉及 MMP-2 和 -7、FAK、ROCK1 和 Rho A 的基因表达抑制。综上所述,上述数据表明,姜黄素的抗癌作用也存在于抑制 N18 细胞的迁移和侵袭,姜黄素可能是开发癌症转移预防剂的有力候选药物。

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