Honokiol inhibits breast cancer cell metastasis by blocking EMT through modulation of Snail/Slug protein translation
Honokiol inhibits breast cancer cell metastasis by blocking EMT through modulation of Snail/Slug protein translation
复制标题
和厚朴酚通过调节 Snail/Slug 蛋白翻译来阻断 EMT，从而抑制乳腺癌细胞转移
DOI：
10.1038/s41401-019-0240-x
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发表时间：
2019-09-01
影响因子：
8.2
通讯作者：
Chen, Shu-zhen
中科院分区：
文献类型：
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作者：
Wang, Wen-die;Shang, Yue;Chen, Shu-zhen
厚朴酚（HNK）是从传统中药厚朴中分离得到的一种有效成分，具有很强的抗肿瘤活性。在本研究中，我们研究了HNK在体外和体内对乳腺癌转移的影响，以及潜在的分子机制。我们发现，HNK（10-70 μ mol/L）剂量依赖性地抑制人乳腺上皮肿瘤细胞系MCF 7，MDA-MB-231和小鼠乳腺肿瘤细胞系4 T1的活力。在transwell和划痕迁移实验中，HNK（10、20、30 μ mol/L）呈剂量依赖性地抑制乳腺癌细胞的侵袭和迁移。我们证明，HNK（10-50 μ mol/L）剂量依赖性地上调上皮标志物E-cadherin和下调间充质标志物，如蜗牛，蛞蝓，和波形蛋白在蛋白水平上在乳腺癌细胞。使用嘌呤霉素掺入试验，我们表明HNK降低了乳腺癌细胞中Snail的翻译效率。在肿瘤转移的小鼠模型中，给予HNK（每天50 mg/kg，腹膜内（i. p.），每周6次，持续30天）显著减少了转移性4 T1细胞来源的结节的数量，并改善了肺中的组织学改变。此外，HNK治疗的小鼠在转移性结节中表现出Snail表达降低和E-cadherin表达增加。总之，HNK通过在mRNA翻译水平下调Snail和Slug蛋白表达来抑制乳腺癌细胞中的EMT。HNK具有通过靶向EMT作为治疗乳腺癌的整合药物的潜力。
Honokiol (HNK), an active compound isolated from traditional Chinese medicine Magnolia officinalis, has shown potent anticancer activities. In the present study, we investigated the effects of HNK on breast cancer metastasis in vitro and in vivo, as well as the underlying molecular mechanisms. We showed that HNK (10-70 mu mol/L) dose-dependently inhibited the viability of human mammary epithelial tumor cell lines MCF7, MDA-MB-231, and mouse mammary tumor cell line 4T1. In the transwell and scratch migration assays, HNK (10, 20, 30 mu mol/L) dose-dependently suppressed the invasion and migration of the breast cancer cells. We demonstrated that HNK (10-50 mu mol/L) dose-dependently upregulated the epithelial marker E-cadherin and downregulated the mesenchymal markers such as Snail, Slug, and vimentin at the protein level in breast cancer cells. Using a puromycin incorporation assay, we showed that HNK decreased the Snail translation efficiency in the breast cancer cells. In a mouse model of tumor metastasis, administration of HNK (50 mg/kg every day, intraperitoneal (i.p.), 6 times per week for 30 days) significantly decreased the number of metastatic 4T1 cell-derived nodules and ameliorated the histological alterations in the lungs. In addition, HNK-treated mice showed decreased Snail expression and increased E-cadherin expression in metastatic nodules. In conclusion, HNK inhibits EMT in the breast cancer cells by downregulating Snail and Slug protein expression at the mRNA translation level. HNK has potential as an integrative medicine for combating breast cancer by targeting EMT.