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Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer

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Radiotherapy is an effective treatment for esophageal cancer; however, tumor resistance to radiation remains a major biological problem. The present study aimed to investigate whether inhibition of autophagy may decrease overall tumor resistance to radiation. The effects of the autophagy inhibitor 3methyladenine (3MA) on radiosensitivity were tested in the EC9706 human esophageal squamous cell carcinoma cell line by colony formation assay. Furthermore, the synergistic cytotoxic effects of 3MA and radiation were assessed in a tumor xenograft model in nude mice. Mechanistic studies were performed using flow cytometry, immunohistochemistry and western blot analysis. The results of the present study demonstrated that radiation induced an accumulation of autophagosomes and 3MA effectively inhibited radiationinduced autophagy. Inhibition of autophagy was shown to significantly increase the radiosensitivity of the tumors in vitro and in vivo. The enhancement ratio of sensitization in EC9706 cells was 1.76 when the cells were treated with 10 mM 3MA, alongside ionizing radiation. In addition, autophagy inhibition increased apoptosis and reduced tumor cell proliferation. The combination of radiation and autophagy inhibition resulted in a significant reduction in tumor volume and vasculature in the murine model. The present study demonstrated in vitro and in vivo that radiationinduced autophagy has a protective effect against cell death, and inhibition of autophagy is able to enhance the radiosensitivity of esophageal squamous cell carcinoma.
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Document Type: Research Article

Affiliations: 1: Department of Radiation Oncology, Zhengzhou University Affiliated Cancer Hospital, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China 2: Department of Pathology, Zhengzhou University Affiliated Cancer Hospital, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China 3: Department of Radiation Oncology, Zhengzhou People's Hospital, Zhengzhou, Henan 450053, P.R. China 4: Department of Pathology, Zhengzhou University Affiliated Zhengzhou Central Hospital, Zhengzhou, Henan 450003, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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