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水飞蓟宾通过p38丝裂原活化蛋白激酶信号通路下调基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的表达,从而抑制人胃癌SGC7901细胞的迁移和侵袭。

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.

作者信息

Lu Shuming, Zhang Zhuqing, Chen Meiru, Li Chunyan, Liu Lina, Li Yan

机构信息

Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.

Department of Pathology, Dalian Municipal Central Hospital, Dalian, Liaoning 116033, P.R. China.

出版信息

Oncol Lett. 2017 Dec;14(6):7577-7582. doi: 10.3892/ol.2017.7080. Epub 2017 Sep 27.

Abstract

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.

摘要

本研究的目的是观察水飞蓟宾和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,并探讨其潜在的相关机制。采用划痕实验、Transwell实验和基质胶侵袭实验研究水飞蓟宾对细胞迁移和侵袭的影响。采用蛋白质免疫印迹分析(Western blot分析)测定p38丝裂原活化蛋白激酶(p38MAPK)、磷酸化(p-)p38丝裂原活化蛋白激酶、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,水飞蓟宾以剂量依赖的方式抑制人胃癌SGC7901细胞的迁移能力。此外,基质胶侵袭实验和Transwell迁移实验显示,水飞蓟宾与SB203580联合处理显著减少了侵袭细胞的数量。蛋白质免疫印迹分析表明,p38丝裂原活化蛋白激酶的磷酸化水平降低,而p-38丝裂原活化蛋白激酶的表达没有明显变化。此外,在水飞蓟宾、SB203580以及水飞蓟宾与SB203580联合处理组中,MMP-2和MMP-9的表达均显著降低。综上所述,水飞蓟宾通过抑制p38丝裂原活化蛋白激酶信号级联反应,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。

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