Zhou Long Dian, Xiong Xu, Long Xin Hua, Liu Zhi Li, Huang Shan Hu, Zhang Wei
Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Department of Respiratory Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Oncol Lett. 2014 Nov;8(5):2063-2068. doi: 10.3892/ol.2014.2464. Epub 2014 Aug 20.
Accumulating evidence has revealed that an elevated expression level of Aurora-B is associated with metastasis in various types of malignant tumor. However, it is currently unclear whether this molecule is involved in non-small lung cancer (NSCLC) metastasis, and the molecular mechanisms associated with Aurora-B and metastasis remain unknown. In the present study, in order to investigate whether Aurora-B is involved in the development and metastasis of NSCLC, the Aurora-B protein expression in NSCLC tissues was detected by immunohistochemistry and its association with metastasis was analyzed. The results revealed that the expression levels of the Aurora-B protein in tissues obtained from NSCLC patients with lymph node metastasis were significantly higher than those without metastatic disease. Furthermore, the effect of Aurora-B inhibition on A549 cell migration and invasion, as well as the activity of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway was evaluated. Aurora-B was inhibited in the A549 cells using short hairpin RNA, and the cell migration and invasion rates were investigated using wound healing and Transwell invasion assays. In addition, the expression of the main proteins in the PI3K/Akt/nuclear factor-κB (NF-κB) signaling pathway, and matrix metalloproteinase (MMP)-2 and -9 were measured by western blot analysis. The results demonstrated that cell migration and invasion were decreased as a result of silencing Aurora-B. Furthermore, the activity of the PI3K/Akt/NF-κB signaling pathway and the expression of MMP-2 and -9 protein were suppressed by silencing Aurora-B. The results of the present study indicate that the knockdown of Aurora-B suppresses A549 cell invasion and migration via the inhibition of the PI3K/Akt signaling pathway and thus, targeting Aurora-B may present a potential treatment strategy for NSCLC.
越来越多的证据表明，Aurora-B表达水平升高与多种恶性肿瘤的转移有关。然而，目前尚不清楚该分子是否参与非小细胞肺癌（NSCLC）的转移，且与Aurora-B和转移相关的分子机制仍不清楚。在本研究中，为了探究Aurora-B是否参与NSCLC的发生和转移，采用免疫组织化学方法检测NSCLC组织中Aurora-B蛋白的表达，并分析其与转移的关系。结果显示，有淋巴结转移的NSCLC患者组织中Aurora-B蛋白的表达水平显著高于无转移疾病的患者。此外，评估了抑制Aurora-B对A549细胞迁移和侵袭以及磷酸肌醇3激酶（PI3K）/Akt信号通路活性的影响。使用短发夹RNA抑制A549细胞中的Aurora-B，并通过伤口愈合和Transwell侵袭试验研究细胞迁移和侵袭率。此外，通过蛋白质印迹分析检测PI3K/Akt/核因子-κB（NF-κB）信号通路中主要蛋白以及基质金属蛋白酶（MMP）-2和-9的表达。结果表明，沉默Aurora-B可导致细胞迁移和侵袭减少。此外，沉默Aurora-B可抑制PI3K/Akt/NF-κB信号通路的活性以及MMP-2和-9蛋白的表达。本研究结果表明，敲低Aurora-B可通过抑制PI3K/Akt信号通路抑制A549细胞的侵袭和迁移，因此，靶向Aurora-B可能是NSCLC的一种潜在治疗策略。
