Radiation-induced autophagy promotes esophageal squamous cell carcinoma cell survival via the LKB1 pathway

Lu,Chi; Xie,Conghua

doi:10.3892/or.2016.4753

June-2016 Volume 35 Issue 6

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June-2016 Volume 35 Issue 6

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Article

Radiation-induced autophagy promotes esophageal squamous cell carcinoma cell survival via the LKB1 pathway

Authors:
- Chi Lu
- Conghua Xie
View Affiliations / Copyright

Affiliations: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430014, P.R. China
Pages: 3559-3565
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Published online on: April 19, 2016

https://doi.org/10.3892/or.2016.4753
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Abstract

Radiotherapy is an important treatment modality for esophageal cancer; however, the clinical efficacy of radiotherapy is limited by tumor radioresistance. In the present study, we explored the hypothesis that radiation induces tumor cell autophagy as a cytoprotective adaptive response, which depends on liver kinase B1 (LKB1) also known as serine/threonine kinase 11 (STK11). Radiation-induced Eca-109 cell autophagy was found to be dependent on signaling through the LKB1 pathway, and autophagy inhibitors that disrupted radiation-induced Eca-109 cell autophagy increased cell cycle arrest and cell death in vitro. Inhibition of autophagy also reduced the clonogenic survival of the Eca-109 cells. When treated with radiation alone, human esophageal carcinoma xenografts showed increased LC3B and p-LKB1 expression, which was decreased by the autophagy inhibitor chloroquine. In vivo inhibition of autophagy disrupted tumor growth and increased tumor apoptosis when combined with 6 Gy of ionizing radiation. In summary, our findings elucidate a novel mechanism of resistance to radiotherapy in which radiation-induced autophagy, via the LKB1 pathway, promotes tumor cell survival. This indicates that inhibition of autophagy can serve as an adjuvant treatment to improve the curative effect of radiotherapy.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Radiation-induced autophagy promotes esophageal squamous cell carcinoma cell survival via the LKB1 pathway

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