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2-羟基-6-十三烷基苯甲酸的抗迁移和抗入侵作用与其通过激活 AMPK 信号通路增强三阴性乳腺癌细胞中 CYP1B1 表达有关。

Anti-migration and anti-invasion effects of 2-hydroxy-6-tridecylbenzoic acid is associated with the enhancement of CYP1B1 expression through activating the AMPK signaling pathway in triple-negative breast cancer cells.

机构信息

College of Food Science and Technology, Shenyang Agricultural University, Shenyang, China.

College of Food Science and Engineering, Bohai University, Jinzhou, China.

出版信息

Nat Prod Res. 2021 Dec;35(24):5924-5928. doi: 10.1080/14786419.2020.1803310. Epub 2020 Aug 11.

DOI:10.1080/14786419.2020.1803310
PMID:32779484
Abstract

2-hydroxy-6-tridecylbenzoic acid is alkylsalicylic acid monomer compound, abundantly existed in the ginkgo biloba extracts, however, the underlying mechanism of its anti-migration and anti-invasion effects in triple-negative breast cancer (TNBC) is not clear. Here, 2-hydroxy-6 -tridecylbenzoic acid inhibited MDA-MB-231 and 4 T-1 cells growth without toxicity to MCF-10A normal breast cells. Meanwhile, 2-hydroxy-6-tridecylbenzoic acid inhibited cells migration and invasion as well as EMT with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, Vimentin, Snail, MMP-2 and MMP-9 expression. The inhibition was further demonstrated by the enhancement of cytochrome P450 (CYP) 1B1 expression through the activation of AMP activated protein kinase (AMPK) in MDA-MB-231 and 4 T-1 cells. Silencing of CYP1B1 and AMPK with siRNA blocked the inhibitory effects of migration and invasion, and reversed the EMT related genes. These findings may provide a novel mechanism of the 2-hydroxy-6-tridecylbenzoic acid as a molecular-targeted therapeutic drug for TNBC patients.

摘要

2-羟基-6-十三烷基苯甲酸是烷基水杨酸单体化合物,大量存在于银杏叶提取物中,但它在三阴性乳腺癌(TNBC)中的抗迁移和抗侵袭作用的潜在机制尚不清楚。在这里,2-羟基-6-十三烷基苯甲酸抑制 MDA-MB-231 和 4T-1 细胞的生长,而对 MCF-10A 正常乳腺细胞没有毒性。同时,2-羟基-6-十三烷基苯甲酸抑制细胞迁移和侵袭,以及 EMT,伴随着 E-钙黏蛋白表达的增加,N-钙黏蛋白、波形蛋白、Snail、MMP-2 和 MMP-9 表达的减少。这种抑制作用通过激活 MDA-MB-231 和 4T-1 细胞中的 AMP 激活蛋白激酶(AMPK)来增强细胞色素 P450(CYP)1B1 的表达进一步得到证实。用 siRNA 沉默 CYP1B1 和 AMPK 可阻断迁移和侵袭的抑制作用,并逆转 EMT 相关基因。这些发现可能为 2-羟基-6-十三烷基苯甲酸作为 TNBC 患者的靶向治疗药物提供了一种新的机制。

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