β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers.
β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers.
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β-拉帕酮通过抑制 NQO1 阳性乳腺癌的上皮间质转化来抑制肿瘤进展
DOI：
10.1038/s41598-017-02937-0
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发表时间：
2017-06-02
影响因子：
4.6
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Yang Y;Zhou X;Xu M;Piao J;Zhang Y;Lin Z;Chen L
NQO 1是一种FAD结合蛋白，可以形成同源二聚体并将醌还原为氢醌，目前越来越多的证据表明，NQO 1在实体癌中显着升高。在这里，我们证明了NQO 1在乳腺癌中升高，其表达水平与浸润和降低的无病生存率（DFS）和总生存率（OS）呈正相关。接下来，我们发现β-拉帕酮由于其对NQO 1表达的影响而在乳腺癌细胞系中发挥显著的抗增殖和抗转移作用。此外，我们发现β-拉帕醌的抗癌作用是通过Akt/mTOR通路的失活介导的。总之，这些结果表明，NQO 1可能是乳腺癌患者有用的预后生物标志物，其生物活化药物β-拉帕醌代表了一个有前途的新发展和指示NQO 1阳性乳腺癌进展的有效策略。
NQO1 is a FAD-binding protein that can form homodimers and reduce quinones to hydroquinones, and a growing body of evidence currently suggests that NQO1 is dramatically elevated in solid cancers. Here, we demonstrated that NQO1 was elevated in breast cancer and that its expression level was positively correlated with invasion and reduced disease free survival (DFS) and overall survival (OS) rates. Next, we found that β-lapachone exerted significant anti-proliferation and anti-metastasis effects in breast cancer cell lines due to its effects on NQO1 expression. Moreover, we revealed that the anti-cancer effects of β-lapachone were mediated by the inactivation of the Akt/mTOR pathway. In conclusion, these results demonstrated that NQO1 could be a useful prognostic biomarker for patients with breast cancer, and its bioactivatable drug, β-lapachone represented a promising new development and an effective strategy for indicating the progression of NQO1-positive breast cancers.