LKB1 promotes radioresistance in esophageal cancer cells exposed to radiation, by suppression of apoptosis and activation of autophagy via the AMPK pathway

He,Qing; Li,Jing; Dong,Feng; Cai,Chuanshu; Zou,Xi

doi:10.3892/mmr.2017.6852

LKB1 promotes radioresistance in esophageal cancer cells exposed to radiation, by suppression of apoptosis and activation of autophagy via the AMPK pathway

Authors:
- Qing He
- Jing Li
- Feng Dong
- Chuanshu Cai
- Xi Zou
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Affiliations: Department of Radiotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China, Department of Radiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
Published online on: June 23, 2017 https://doi.org/10.3892/mmr.2017.6852
Pages: 2205-2210

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Abstract

Liver kinase B (LKB) 1 acts as a tumor suppressor in a broad spectrum of human cancers, and is important in chemoradiotherapy treatment of various tumor types. However, the potential function of LKB1 in esophageal cancer radiotherapy remains to be elucidated. The aim of the present study was to investigate the role of LKB1 in radiosensitivity of esophageal cancer in vivo and in vitro, and to explore its molecular mechanism. Eca‑109 cells transfected with LKB1 overexpression plasmid were xenografted into nude mice and subjected to irradiation and it was observed that the tumor volume was significantly increased in LKB1‑overexpressed tumors compared with that of the control tumors. The in vitro study revealed that LKB1 overexpression led to the radioresistance of Eca‑109 cells, as determined by MTT and colony formation assays. Furthermore, it was demonstrated that LKB1 overexpression inhibited apoptosis and activated autophagy of Eca‑109 cells following radiation treatment, as determined by flow cytometry and western blot analyses. AMP‑activated protein kinase (AMPK) inhibition attenuated LKB1‑induced radioresistance of Eca‑109 cells. To the best of our knowledge, the present study, for the first time, confirmed that LKB1 induces radioresistance of esophageal cancer cells to irradiation via suppression of apoptosis and activation of autophagy, and AMPK mediates this function of LKB1 in esophageal cancer radiotherapy. These findings suggest that LKB1 may act as a novel target in the future, to maximize the efficiency of esophageal cancer radiotherapy.

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