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A new gallium complex inhibits tumor cell invasion and matrix metalloproteinase MMP-14 expression and activity
Metallomics ( IF 3.4 ) Pub Date : 2017-07-18 00:00:00 , DOI: 10.1039/c7mt00049a
Ahmed Mohsen 1, 2, 3, 4, 5 , Philippe Collery 5, 6, 7 , Roselyne Garnotel 8, 9, 10, 11, 12 , Bertrand Brassart 8, 9, 10, 11, 12 , Nicolas Etique 8, 9, 10, 11, 12 , Gilane Mohamed Sabry 13, 14, 15, 16, 17 , Rasha Elsherif Hassan 13, 14, 15, 16, 17 , Pierre Jeannesson 13, 14, 15, 16, 17 , Didier Desmaële 1, 2, 3, 4, 5 , Hamid Morjani 8, 9, 10, 11, 12
Affiliation  

In this study, we investigated the effect of [N-(5-chloro-2-hydroxyphenyl)-L-aspartato] chlorogallate (GS2), a new water soluble gallium complex, on cell invasion and on the expression and activity of matrix metalloproteinases (MMPs) in human metastatic HT-1080 fibrosarcoma and MDA-MB 231 breast carcinoma cells. The effect on cell invasion was studied using a modified Boyden chamber coated with a type-I collagen. We analyzed the effect of GS2 on MMP-2, MMP-9, and MMP-14 via zymography and enzymatic assay using high affinity fluorogenic substrates. The expression of MMP mRNA was analyzed via qRT-PCR. GS2 induced a decrease in cell invasion. A dose-dependent inhibition effect was observed on the activities of MMP-2, MMP-9, and MMP-14 with the IC50 values of 168, 82, and 20 μM, respectively. A decrease in the expression of MMP-14 mRNA was observed in both cell lines, whereas the expression of MMP-2 and MMP-9 mRNA was decreased only in the MDA-MB231 cells. Data obtained for the expression of MMP-14 mRNA were confirmed via Western blotting. In fact, MMP-14 expression was decreased in the presence of GS2. Overall, these data show that GS2 is a promising compound for anti-invasive and anticancer therapy.

中文翻译:

一种新的镓复合物抑制肿瘤细胞的侵袭和基质金属蛋白酶MMP-14的表达和活性

在这项研究中,我们研究了[ N-(5-氯-2-羟基苯基)-L-天冬氨酸]氯镓酸盐(GS2),一种新型的水溶性镓配合物,对细胞侵袭以及基质金属蛋白酶的表达和活性的影响。 (MMPs)在人类转移性HT-1080纤维肉瘤和MDA-MB 231乳腺癌细胞中。使用涂有I型胶原的改良Boyden腔室研究了对细胞侵袭的影响。我们使用高亲和力的荧光底物通过酶谱和酶法分析了GS2对MMP-2,MMP-9和MMP-14的影响。MMP mRNA的表达通过定量RT-PCR。GS2诱导细胞侵袭的减少。观察到对MMP-2,MMP-9和MMP-14活性的剂量依赖性抑制作用,IC 50值分别为168、82和20μM。在两种细胞系中均观察到MMP-14 mRNA的表达降低,而MMP-2和MMP-9 mRNA的表达仅在MDA-MB231细胞中降低。通过Western印迹证实获得的关于MMP-14mRNA表达的数据。实际上,在GS2存在下,MMP-14表达降低。总体而言,这些数据表明,GS2是用于抗侵袭和抗癌治疗的有前途的化合物。
更新日期:2017-08-03
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