Silibinin inhibits the migration and invasion of human gastric cancer SGC7901 cells by downregulating MMP-2 and MMP-9 expression via the p38MAPK signaling pathway
Silibinin inhibits the migration and invasion of human gastric cancer SGC7901 cells by downregulating MMP-2 and MMP-9 expression via the p38MAPK signaling pathway
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DOI：
10.3892/ol.2017.7080
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发表时间：
2017-12-01
期刊：
影响因子：
2.9
通讯作者：
Li, Yan
中科院分区：
文献类型：
--
作者：
Lu, Shuming;Zhang, Zhuqing;Li, Yan
本研究旨在观察水飞蓟宾和p38丝裂原活化蛋白激酶（MAPK）信号通路抑制剂SB203580对SGC7901细胞迁移和侵袭能力的影响，并探讨其相关机制。采用Scratch、Transwell和Matrigel侵袭实验研究水飞蓟宾对细胞迁移和侵袭的影响。Western blot检测p38MAPK、磷酸化（p-） p38MAPK、基质金属蛋白酶(MMP)-2和MMP-9的表达水平。在基因组水平上，采用定量聚合酶链反应评估MMP-2和MMP-9的表达水平。划痕实验结果表明水飞蓟宾对人胃癌SGC7901细胞的迁移能力有一定的抑制作用，并呈剂量依赖性。此外，Matrigel侵袭和Transwell迁移实验显示，水飞蓟宾和SB203580联合处理显著减少了侵袭细胞的数量。Western blot分析显示p38MAPK的磷酸化降低，但p38MAPK的表达没有明显变化。此外，水飞蓟宾、SB203580以及水飞蓟宾与SB203580合用时，MMP-2和MMP-9的表达均显著降低。综上所述，水飞蓟宾素通过抑制p38MAPK信号级联，下调MMP-2和MMP-9的表达，从而降低SGC7901细胞的侵袭和迁移能力。
The objective of the present study was to observe the effects of silibinin and the p38 mitogen-activated protein kinase (MAPK) signaling pathway inhibitor SB203580 on the migration and invasion capabilities of SGC7901 cells, and to explore the underlying associated mechanisms. Scratch, Transwell and Matrigel invasion assays were performed to study the effects of silibinin on cell migration and invasion. Western blot analysis was used to determine the expression levels of p38MAPK, phosphorylated (p-) p38MAPK, matrix metalloproteinase (MMP)-2 and MMP-9. At the genomic level, quantitative polymerase chain reaction was performed to evaluate the expression levels of MMP-2 and MMP-9. The results of scratch assay indicated that silibinin inhibited the migration capabilities of human gastric cancer SGC7901 cells in a dose-dependent manner. Additionally, Matrigel invasion and Transwell migration assays revealed that silibinin and SB203580 combined treatment significantly reduced the number of invasive cells. Western blot analysis indicated a reduced phosphorylation of p38MAPK without marked changes in p38MAPK expression. In addition, the expression of MMP-2 and MMP-9 significantly decreased in the presence of silibinin, SB203580, and the combination of silibinin and SB203580. In summary, silibinin decreased the invasion and migration abilities of SGC7901 cells by downregulating the expression of MMP-2 and MMP-9 through inhibiting p38MAPK signaling cascades.