Inhibitory effect of chitooligosaccharides on matrix metalloproteinase-9 in human fibrosarcoma cells (HT1080)

Inhibitory effect of chitooligosaccharides on matrix metalloproteinase-9 in human fibrosarcoma cells (HT1080)
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DOI:
10.1007/s10126-006-6031-7
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发表时间:
2006-11-01
影响因子:
3
通讯作者:
Kim, Se-Kwon
Kim, Se-Kwon
中科院分区:
生物学2区
文献类型:
--
作者:
Van Ta, Quang;Kim, Moon-Moo;Kim, Se-Kwon

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基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)具有明胶酶活性,在肿瘤的侵袭和转移中起重要作用。因此,抑制特定类型的MMP(包括MMP-9)已成为治疗干预的有吸引力的靶标。本研究旨在探讨壳寡糖(COS)对HT 1080细胞MMP-9活性及表达的影响。采用明胶酶谱法、逆转录-聚合酶链反应(RT-PCR)、基因报告分析和Western印迹分析检测不同分子量COS的抑制作用。在明胶酶谱中清楚地观察到COS存在下的MMP-9抑制。具体地,1-至3-kDa COS(COS-I)表现出最高的抑制作用,MMP-9的活性在HT 1080细胞中测试的分子量级分。COS-I可抑制MMP-9基因和蛋白表达(P < 0.01)。这些结果表明,低分子量COS可以被认为是一种有效的MMP-9抑制剂。
Matrix metalloproteinase-9 (MMP-9) has gelatinase activity and plays an important role in cancer invasion and metastasis. Therefore, inhibition of specific types of MMPs including MMP-9 has become an attractive target for therapeutic intervention. The aim of this study was to investigate the effect of chitooligosaccharides (COS) on activity and expression of MMP-9 in HT1080 cells. The inhibitory effect of COS with different molecular masses was examined by gelatin zymography, reverse transcriptase-polymerase chain reaction (RT-PCR), gene reporter assay, and Western blot analysis. MMP-9 inhibition in the presence of COS was clearly observed in gelatin zymography. Specifically, 1- to 3-kDa COS (COS-I) exhibited the highest inhibitory effect on MMP-9 activity in HT1080 cells among tested molecular mass fractions. It was also found that COS-I was capable of inhibiting both gene and protein expression of MMP-9 (P < 0.01). These results suggest that low molecular mass COS can be considered as a potent inhibitor of MMP-9.