Shikonin inhibits tumor invasion via down-regulation of NF-κB-mediated MMP-9 expression in human ACC-M cells
Shikonin inhibits tumor invasion via down-regulation of NF-κB-mediated MMP-9 expression in human ACC-M cells
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DOI：
10.1111/j.1601-0825.2010.01758.x
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发表时间：
2011-05-01
期刊：
影响因子：
3.8
通讯作者：
Chenping, Z.
中科院分区：
文献类型：
--
作者：
Min, R.;Zun, Z.;Chenping, Z.
目的：研究紫草素对人高转移性腺样囊性癌(ACC-M)细胞的抗侵袭作用，并探讨其可能的分子机制。方法：紫草素(0，2.5，5，10mU M)作用于ACC-M细胞24 h，分别用Western印迹和明胶酶谱检测细胞内基质金属蛋白酶-2和基质金属蛋白酶-9的蛋白表达水平和明胶溶解活性。Matrigel侵袭实验检测肿瘤侵袭潜能，电迁移率改变实验检测核因子-kappa B活性。结果：紫草素作用于ACC-M细胞24 h后，细胞侵袭力呈剂量依赖性降低，10 mU M的紫草素无细胞毒作用。随着紫草素浓度的增加，基质金属蛋白酶-9的蛋白水平和明胶溶解活性明显受到抑制。结论：紫草素可能通过下调ACC-M细胞中的基质金属蛋白酶-9的表达，从而抑制肿瘤的侵袭。紫草素抑制核因子-kappaB介导的基质金属蛋白酶-9的表达可能是未来ACC患者的一种强有力的治疗选择。
Objective:The aim of this study was to examine the anti-invasion effect of Shikonin on human high-metastatic adenoid cystic carcinoma (ACC-M) cells and to explain the possible molecular mechanism involved.Methods:The ACC-M cells were treated with Shikonin (0, 2.5, 5, 10 mu M) for 24 h. The protein levels and gelatinolytic activities of MMP-2 and MMP-9 were analyzed using Western blot and Gelatin zymography test, respectively. Matrigel invasion assays were used to investigate tumor invasive potential and electromobility shift assays were used to determine the activity of NF-kappa B.Results:The invasiveness of ACC-M cells was reduced in a dose dependent manner following 24-h treatment of up to 10 mu M of the Shikonin at which concentration no cytotoxicity occurred. The protein levels and gelatinolytic activities of MMP-9 were significantly suppressed by increasing Shikonin concentrations. The down-regulation of MMP-9 appeared to be via the inactivation of NF-kappa B as the treatment with Shikonin suppressed the protein level of phosphate-IkBa, which was accompanied by a decrease in DNA-binding level of the factor.Conclusions:Shikonin inhibits tumor invasion via downregulation of MMP-9 expression in ACC-M cells. Pharmacologic inhibition of the NF-kappa B-mediated MMP-9 expression by Shikonin might be a powerful treatment option for ACC patients in future.