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汉黄芩素通过抑制 5-脂氧合酶/白三烯 B2 受体(5-LO/BLT2)级联反应抑制 LPS 增强的 MDA-MB-231 乳腺癌细胞的侵袭性。

Wogonin suppresses the LPS‑enhanced invasiveness of MDA‑MB‑231 breast cancer cells by inhibiting the 5‑LO/BLT2 cascade.

机构信息

College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.

Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju‑si, Chungbuk 28116, Republic of Korea.

出版信息

Int J Mol Med. 2018 Oct;42(4):1899-1908. doi: 10.3892/ijmm.2018.3776. Epub 2018 Jul 12.

Abstract

Wogonin, a naturally occurring bioactive monoflavonoid isolated from Scutellariae radix (roots of Scutellariae baicalensis Georgi), has known anticancer effects. However, the molecular signaling mechanism by which wogonin inhibits invasiveness in breast cancer cells remains unclear. In the present study, it was observed that wogonin exerted an inhibitory effect on the lipopolysaccharide (LPS)‑enhanced invasiveness of MDA‑MB‑231 cells. In addition, wogonin inhibited the synthesis of interleukin‑8 (IL‑8) and matrix metallopeptidase‑9 (MMP‑9), which are critical for promoting invasiveness in MDA‑MB‑231 cells. Wogonin also suppressed the expression of leukotriene B4 receptor 2 (BLT2) and the synthesis of its ligand, by inhibiting 5‑lipoxygenase (5‑LO) in LPS‑stimulated MDA‑MB‑231 cells. Notably, wogonin attenuated the production of IL‑8 and MMP‑9 by inhibiting the BLT2/extracellular signal‑regulated kinase (ERK)‑linked cascade. Finally, in vivo, LPS‑driven MDA‑MB‑231 cell metastasis was markedly suppressed by wogonin administration. Overall, the present results suggested that wogonin inhibited the 5‑LO/BLT2/ERK/IL‑8/MMP‑9 signaling cascade and demonstrated that this cascade may be an important target through which wogonin exerts its anticancer effects in breast cancer.

摘要

汉黄芩素是从黄芩根(黄芩)中分离得到的一种天然生物活性单黄酮,具有抗癌作用。然而,汉黄芩素抑制乳腺癌细胞侵袭性的分子信号机制尚不清楚。本研究观察到汉黄芩素对脂多糖(LPS)增强的 MDA-MB-231 细胞侵袭性有抑制作用。此外,汉黄芩素抑制白细胞介素-8(IL-8)和基质金属蛋白酶-9(MMP-9)的合成,这对于促进 MDA-MB-231 细胞的侵袭性至关重要。汉黄芩素还通过抑制 LPS 刺激的 MDA-MB-231 细胞中的 5-脂氧合酶(5-LO)来抑制白三烯 B4 受体 2(BLT2)的表达及其配体的合成。值得注意的是,汉黄芩素通过抑制 BLT2/细胞外信号调节激酶(ERK)级联反应来减弱 IL-8 和 MMP-9 的产生。最后,在体内,汉黄芩素给药明显抑制了 LPS 驱动的 MDA-MB-231 细胞转移。综上所述,本研究结果表明,汉黄芩素抑制 5-LO/BLT2/ERK/IL-8/MMP-9 信号通路,表明该通路可能是汉黄芩素在乳腺癌中发挥抗癌作用的重要靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3a3/6108877/e3f112185334/IJMM-42-04-1899-g00.jpg

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