Altered Wnt5a expression affects radiosensitivity of non‑small cell lung cancer via the Wnt/β‑catenin pathway

Li,Junzhe; Xu,Shijie; Dong,Hua; Wu,Xiayu; Wang,Li-Hong; Xu,Xianhua

doi:10.3892/etm.2021.10927

Altered Wnt5a expression affects radiosensitivity of non‑small cell lung cancer via the Wnt/β‑catenin pathway

Authors:
- Junzhe Li
- Shijie Xu
- Hua Dong
- Xiayu Wu
- Li-Hong Wang
- Xianhua Xu
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Affiliations: Department of Thoracic Surgery, Hainan Cancer Hospital, Affiliated Cancer Hospital of Hainan Medical University, Haikou, Hainan 570312, P.R. China, Medical Research Center, Hainan Cancer Hospital, Affiliated Cancer Hospital of Hainan Medical University, Haikou, Hainan 570312, P.R. China, Hainan Cancer Prevention and Treatment Center, Hainan Cancer Hospital, Affiliated Cancer Hospital of Hainan Medical University, Haikou, Hainan 570312, P.R. China, Department of Pathology, Hainan Cancer Hospital, Affiliated Cancer Hospital of Hainan Medical University, Haikou, Hainan 570312, P.R. China
Published online on: October 26, 2021 https://doi.org/10.3892/etm.2021.10927
Article Number: 5
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It has been reported that upregulation of wingless‑type protein 5a (Wnt5a) is associated with poor prognosis in patients with non‑small cell lung cancer (NSCLC). Wnt5a expression is often upregulated in radiation‑resistant NSCLC cells. However, the biological functions or molecular mechanisms of radiosensitivity in NSCLC remain unknown. In the present study, MTT assay and flow cytometric analysis were performed to assess the effect of overexpression or knockdown of Wnt5a and/or radiation on the proliferation and apoptosis of NSCLC cells. Furthermore, western blot analysis was performed to detect canonical Wnt signaling (β‑catenin) in H1650 and A549 cells. The results demonstrated that Wnt5a knockdown combined with irradiation inhibited proliferation and induced apoptosis in NSCLC cells compared with Wnt5a knockdown or radiotherapy alone. In addition, the combination of Wnt5a knockdown and irradiation decreased nuclear and increased cytoplasmic β‑catenin expression in H1650 and A549 cells, the effects of which were reversed following overexpression of Wnt5a. The combination of overexpressing Wnt5a and irradiation resulted in significant tumor regression, while β‑catenin knockdown reversed Wnt5a overexpression‑induced NSCLC cell proliferation. Taken together, these results suggest that Wnt5a may be involved in the activation of β‑catenin‑dependent canonical Wnt signaling, and thus may influence the effectiveness of radiation therapy in NSCLC.

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