XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway

Li,Chong; Zheng,Xu; Han,Yanyan; Lv,Yan; Lan,Fu; Zhao,Jie

doi:10.3892/ol.2018.8491

XAV939 inhibits the proliferation and migration of lung adenocarcinoma A549 cells through the WNT pathway

Authors:
- Chong Li
- Xu Zheng
- Yanyan Han
- Yan Lv
- Fu Lan
- Jie Zhao
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Affiliations: Department of Pathology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, P.R. China
Published online on: April 13, 2018 https://doi.org/10.3892/ol.2018.8491
Pages: 8973-8982
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study assessed the effects of the tankyrase (TNKS) small molecule inhibitor XAV939 on the proliferation and migration of lung adenocarcinoma A549 cells and the possible underlying mechanism. To do this, the association between TNKS and the WNT/β‑catenin signaling pathway in lung acinar adenocarcinoma was investigated. Immunohistochemistry was performed, which demonstrated that TNKS, β‑catenin and Myc proto‑oncogene protein (c‑Myc) proteins are positively expressed in lung adenocarcinoma tissue; this expression was significantly higher than that in normal adjacent non‑carcinoma tissues. A549 cell proliferation was inhibited in all XAV939‑intervention groups examined. In the wound‑healing assay, cells treated with different concentrations of XAV939 exhibited a significantly increased scratch width compared with the control group. Reverse transcription‑semi‑quantitative polymerase chain reaction analysis revealed that β‑catenin mRNA expression was significantly decreased in A549 cells in response to different XAV939 concentrations compared with the control group. Immunofluorescence revealed that β‑catenin protein, initially localized in the nucleus/cytoplasm, gradually translocated to the cytoplasm/membrane, an effect that was associated with increased drug concentration. TNKS, β‑catenin and c‑Myc protein expression in A549 cells treated with XAV939 was reduced compared with that in untreated cells. Therefore, abnormally high TNKS expression may promote the occurrence of lung cancer. The TNKS inhibitor XAV939 inhibited lung adenocarcinoma A549 cell proliferation and migration in vitro. The underlying mechanism by which XAV939 exerted its inhibitory effects may be associated with attenuation of the WNT signaling pathway.

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