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辣椒素通过降低基质金属蛋白酶-9的表达,经由AMPK/NF-κB信号通路抑制食管鳞状细胞癌的迁移和侵袭。

Capsaicin inhibits the migration and invasion via the AMPK/NF-κB signaling pathway in esophagus sequamous cell carcinoma by decreasing matrix metalloproteinase-9 expression.

作者信息

Guo Yong, Liu Ning, Liu Kun, Gao Min

机构信息

Office of Drug Purchase, Affiliated Hospital of Jining Medical University, Jining 272000, Shandong, China.

Information Technology Centre, Jining Medical University, Jining 272000, Shandong, China.

出版信息

Biosci Rep. 2019 Aug 5;39(8). doi: 10.1042/BSR20190819. Print 2019 Aug 30.

Abstract

Antitumor activity of Capsaicin has been studied in various tumor types, but its potency in esophageal squamous cell carcinoma (ESCC) remains to be elucidated. Here, we explored the molecular mechanism of the capsaicin-induced antitumor effects on ESCC Eca109 cells. Eca109 cells were treated with capsaicin , the migration and invasion capacities were significantly decreased by scratch assay and transwell invasion assay. Meanwhile, matrix metalloproteinase (MMP)-9 (MMP-9) expression levels were also obviously down-regulated by Western blot. However, phosphorylated AMPK levels were significantly up-regulated, and this effect was eliminated by the AMPK inhibitor Compound C treatment. In addition, capsaicin can enhance sirtuin1 (SIRT1) expression, which could activate nuclear factor-κB (NF-κB) through deacetylation, and activate AMPK inducing the phosphorylation of IκBα and nuclear localization of NF-κB p65. Overall, these results revealed that Capsaicin can inhibit the migration and invasion of ESCC cells via the AMPK/NF-κB signaling pathway.

摘要

辣椒素的抗肿瘤活性已在多种肿瘤类型中进行了研究,但其在食管鳞状细胞癌(ESCC)中的效力仍有待阐明。在此,我们探讨了辣椒素对ESCC Eca109细胞抗肿瘤作用的分子机制。用辣椒素处理Eca109细胞,通过划痕试验和Transwell侵袭试验发现其迁移和侵袭能力显著降低。同时,通过蛋白质印迹法也明显下调了基质金属蛋白酶(MMP)-9(MMP-9)的表达水平。然而,磷酸化的AMPK水平显著上调,并且这种效应通过AMPK抑制剂Compound C处理而消除。此外,辣椒素可以增强沉默调节蛋白1(SIRT1)的表达,其可通过去乙酰化激活核因子-κB(NF-κB),并激活AMPK诱导IκBα的磷酸化和NF-κB p65的核定位。总体而言,这些结果表明辣椒素可通过AMPK/NF-κB信号通路抑制ESCC细胞的迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcc6/6682549/1959df7f3b85/bsr-39-bsr20190819-g1.jpg

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