TNFα 暴露的 MDA-MB-231 乳腺癌细胞中 NF-κB 依赖性 CXCR3 和 CXCL10 表达的乙醇提取物抑制作用。

Inhibitory Effect of Ethanolic Extract on NF-κB-Dependent CXCR3 and CXCL10 Expression in TNFα-Exposed MDA-MB-231 Breast Cancer Cells.

机构信息

Department of Biological Sciences, Sanghuh College of Life Sciences, Konkuk University, Seoul 05029, Korea.

Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 05029, Korea.

出版信息

Int J Mol Sci. 2018 Sep 3;19(9):2607. doi: 10.3390/ijms19092607.

CXC motif chemokine ligand 10 (CXCL10) and its receptor CXC motif chemokine receptor 3 (CXCR3), play important roles in the motility of breast cancer cells. is a herb that has been used as a traditional medicine for thousands of years in Korea and China. Whether inhibits the motility of metastatic breast cancer cells is not clear yet. In this study, we show that ethanolic extract (ACE) prevented tumor necrosis factor-alpha (TNFα)-induced migration of MDA-MB-231 cells. ACE significantly attenuated TNFα-induced upregulation of CXCL10 and CXCR3 expression at the gene promoter level. Mechanistically, ACE inhibits TNFα-induced phosphorylation of inhibitor of κB (IκB) kinase (IKK), IκB and p65/RelA, leading to the suppression of nuclear translocation of p65/RelA nuclear factor kappa-B (NF-κB). Also, ACE inhibited NF-κB-dependent and promoter activities. These results suggest that ACE abrogates TNFα-induced migration of MDA-MB-231 breast cancer cells through down-regulation of IKK-NF-κB-dependent and 0 expression. Our results suggest that ACE has potential as a herbal supplement for the inhibition of breast cancer metastasis.

CXC 趋化因子配体 10（CXCL10）及其受体 CXC 趋化因子受体 3（CXCR3）在乳腺癌细胞的迁移中发挥重要作用。淫羊藿是一种在韩国和中国被用作传统药物数千年的草药。淫羊藿是否抑制转移性乳腺癌细胞的迁移尚不清楚。在这项研究中，我们表明淫羊藿乙醇提取物（ACE）可预防肿瘤坏死因子-α（TNFα）诱导的 MDA-MB-231 细胞迁移。ACE 显著减弱了 TNFα 诱导的 CXCL10 和 CXCR3 表达在基因启动子水平上的上调。在机制上，ACE 抑制 TNFα 诱导的 IκB 激酶（IKK）、IκB 和 p65/RelA 的磷酸化，从而抑制 p65/RelA 核因子κB（NF-κB）的核易位。此外，ACE 抑制了 NF-κB 依赖性和启动子活性。这些结果表明 ACE 通过下调 IKK-NF-κB 依赖性和 0 表达来阻断 TNFα 诱导的 MDA-MB-231 乳腺癌细胞迁移。我们的结果表明，ACE 有可能作为抑制乳腺癌转移的草药补充剂。