Reduced RKIP expression levels are associated with frequent non-small cell lung cancer metastasis and STAT3 phosphorylation and activation

Wang,Ansheng; Duan,Guixin; Zhao,Chengling; Gao,Yuan; Liu,Xuegang; Wang,Zuyi; Li,Wei; Wang,Kangwu; Wang,Wei

doi:10.3892/ol.2017.5846

Reduced RKIP expression levels are associated with frequent non-small cell lung cancer metastasis and STAT3 phosphorylation and activation

Authors:
- Ansheng Wang
- Guixin Duan
- Chengling Zhao
- Yuan Gao
- Xuegang Liu
- Zuyi Wang
- Wei Li
- Kangwu Wang
- Wei Wang
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Affiliations: Shandong University School of Medicine, Jinan, Shandong 250100, P.R. China, Department of Thoracic Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, P.R. China, Department of Respiratory Diseases, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, P.R. China, Department of Cardiac Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
Published online on: March 13, 2017 https://doi.org/10.3892/ol.2017.5846
Pages: 3039-3045
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The current study examined the role of Raf kinase inhibitor protein (RKIP) in non‑small cell lung cancer (NSCLC) metastasis. A total of 100 patients with NSCLC were recruited following pathological diagnosis in the First Affiliated Hospital of Bengbu Medical College. The patients were classified and statistically analyzed according to their clinicopathological characteristics and tumor‑node‑metastasis stage. Paired tumor tissue and adjacent non‑tumor tissue samples were subject to pathological diagnosis and western blot analysis. Transient transfection and lentivirus particle vector-mediated RKIP overexpression, small interfering RNA‑mediated silencing, Transwell assays and immunocytochemistry methods were employed to elucidate the role and underlying mechanisms of RKIP and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in NSCLC metastasis. Furthermore, in order to examine the in vivo effects of RKIP, recombinant lentivirus particles containing the RKIP gene were administrated in a mouse NSCLC tumor model via tail vein injection. The results revealed reduced RKIP expression levels in NSCLC tissue compared with corresponding non‑cancer tissue. Additionally, RKIP expression levels were inversely associated with NSCLC intra‑lung, lymph node and long‑distance metastasis. The results also indicated that RKIP was able to block STAT3 activation via phosphorylation and inhibit NSCLC‑cell metastasis in vitro. Furthermore, RKIP knockdown was able to promote STAT3 phosphorylation and cell metastasis in NSCLC cell lines. During in vivo experiments, RKIP overexpression was able to suppress xenograft tumor metastasis in nude mice. Therefore, RKIP may be an important factor in cancer cell metastasis in patients with NSCLC, and RKIP may inhibit NSCLC‑cell invasion by blocking the activation of the JAK/STAT3 signaling pathway.

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