International Journal of Radiation Research

en Methionine deprivation enhances the radiosensitivity of glioma cells and promotes ionizing radiation-induced immunogenic cell death via the endoplasmic reticulum stress signaling pathway Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;">Background: Methionine deprivation (MD) affects protein stability, signaling pathway activation and redox status of cancerous cells. In this study, we investigated the effects of MD on the radiosensitivity and radiation-induced immunogenic death of glioma cells and the underlying mechanism. Materials and Methods: Human glioma cells, U251 and T98G, were cultured in DMEM medium with or without methionine under normoxia or hypoxia (1% O2). Cell proliferation, radiosensitivity, and DNA damage repair were detected by EdU assay, colony formation assay, γ-H2AX immunofluorescence staining and single-cell gel electrophoresis, respectively. Cell apoptosis and surface exposure of calreticulin (CRT) were detected via flow cytometry. The expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3) and P62 and endoplasmic reticulum stress (ERS) pathway-related proteins PKR-like endoplasmic reticulum kinase (PERK) and inositol requiring enzyme 1 alpha (IRE1α) was detected via Western blotting. Results: MD inhibited the proliferation of normoxic or hypoxic glioma cells. MD combined with radiation promoted apoptosis and increased the number of γ-H2AX foci and the percentage of DNA in the tail of the comet. MD enhanced the radiosensitivity of normoxic or hypoxic glioma cells, which was further enhanced when combined with the autophagy inhibitor 3-methyladenine (3-MA). MD enhanced the transformation of LC3 I to LC3 II and decreased the expression of P62. MD also increased radiation-induced CRT exposure, ATP release and PERK and IRE1α phosphorylation. Conclusion: MD enhanced the radiosensitivity of glioma cells by inhibiting DNA repair and promoted ionizing radiation-induced immunogenic cell death through activating the ERS signaling pathway.</div> Methionine, glioma, autophagy, radiosensitivity, immunogenic cell death. 627 639 http://ijrr.com/browse.php?a_code=A-10-1-1554&slc_lang=en&sid=1 S. Yang 7900319475328460034149 7900319475328460034149 No State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, China H. Qin 7900319475328460034150 7900319475328460034150 No Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China X. Jiang 7900319475328460034151 7900319475328460034151 No State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, China X. Xue 7900319475328460034152 7900319475328460034152 No State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, China H. Tan 7900319475328460034153 7900319475328460034153 No State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, China B. Wang 7900319475328460034154 7900319475328460034154 No Department of Oncology, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China T. Sun 7900319475328460034155 7900319475328460034155 No Neurosurgery and Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China W. Yang detachedy@aliyun.com 7900319475328460034156 7900319475328460034156 Yes State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, China