Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, 133002, China.
Department of Internal Medicine, Yanbian University Hospital, Yanji, 133000, China.
Sci Rep. 2017 Jun 2;7(1):2681. doi: 10.1038/s41598-017-02937-0.
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.
NQO1 是一种结合 FAD 的蛋白,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,NQO1 在实体瘤中显著升高。在这里,我们证明 NQO1 在乳腺癌中升高,其表达水平与侵袭性以及降低的无病生存率 (DFS) 和总生存率 (OS) 呈正相关。接下来,我们发现由于对 NQO1 表达的影响,β-拉帕醌在乳腺癌细胞系中表现出显著的抗增殖和抗转移作用。此外,我们揭示了 β-拉帕醌的抗癌作用是通过 Akt/mTOR 通路的失活来介导的。总之,这些结果表明 NQO1 可以作为乳腺癌患者有用的预后生物标志物,其可激活的药物β-拉帕醌代表了一种有前途的新发展,也是指示 NQO1 阳性乳腺癌进展的有效策略。