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桦褐孔菌多糖通过下调NF-κB信号通路抑制MMP-2和MMP-9,从而抑制B16-F10细胞的迁移和侵袭。

Polysaccharide from Inonotus obliquus inhibits migration and invasion in B16-F10 cells by suppressing MMP-2 and MMP-9 via downregulation of NF-κB signaling pathway.

作者信息

Lee Ki Rim, Lee Jong Seok, Kim Young Rae, Song In Gyu, Hong Eock Kee

机构信息

Department of Bioengineering and Technology, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.

出版信息

Oncol Rep. 2014 May;31(5):2447-53. doi: 10.3892/or.2014.3103. Epub 2014 Mar 21.

Abstract

Polysaccharides derived from Inonotus obliquus (PIO) are known to possess multiple pharmacological activities including antitumor activity. However, the possible molecular mechanisms of these activities are unknown. In the present study, we determined the anti-metastatic potential and signaling pathways of PIO in the highly metastatic B16-F10 mouse melanoma cell line in vitro. We found that PIO suppressed the migration and invasive ability of B16-F10 cells and decreased the expression levels and activities of matrix metalloproteinase (MMP)-2 and MMP-9. In addition, PIO decreased the phosphorylation levels of extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK); PIO also decreased the expression level of cyclooxygenase (COX)‑2 and inhibited the nuclear translocation of nuclear factor κB (NF-κB) in B16-F10 melanoma cells. These results suggest that PIO could suppress the invasion and migration of B16-F10 melanoma cells by reducing the expression levels and activities of MMP-2 and MMP-9 through suppressing MAPK, COX-2 and NF-κB signaling pathways.

摘要

源自桦褐孔菌的多糖(PIO)已知具有多种药理活性,包括抗肿瘤活性。然而,这些活性的可能分子机制尚不清楚。在本研究中,我们在体外高度转移性B16-F10小鼠黑色素瘤细胞系中确定了PIO的抗转移潜力和信号通路。我们发现PIO抑制了B16-F10细胞的迁移和侵袭能力,并降低了基质金属蛋白酶(MMP)-2和MMP-9的表达水平及活性。此外,PIO降低了细胞外信号调节蛋白激酶(ERK)、c-Jun氨基末端激酶(JNK)和p38丝裂原活化蛋白激酶(MAPK)的磷酸化水平;PIO还降低了环氧化酶(COX)-2的表达水平,并抑制了B16-F10黑色素瘤细胞中核因子κB(NF-κB)的核转位。这些结果表明,PIO可通过抑制MAPK、COX-2和NF-κB信号通路,降低MMP-2和MMP-9的表达水平及活性,从而抑制B16-F10黑色素瘤细胞的侵袭和迁移。

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