Endoplasmic reticulum stress protects human thyroid carcinoma cell lines against ionizing radiation-induced apoptosis

• Published in: Molecular medicine reports Vol. 11; no. 3; pp. 2341 - 2347
• Main Authors: WU, XIN-YU, FAN, RUI-TAI, YAN, XIN-HUI, CUI, JING, XU, JUN-LING, GU, HAO, GAO, YONG-JU
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.03.2015; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Activating transcription factor 1; Adenosine triphosphatase; Apoptosis; Apoptosis - radiation effects; Cancer; Cancer therapies; Care and treatment; CCAAT/enhancer-binding protein; Cell Line, Tumor; Drug sensitization; Endoplasmic reticulum; endoplasmic reticulum stress; Endoplasmic Reticulum Stress - radiation effects; Evaluation; Gene expression; Health aspects; Humans; Ionizing radiation; Kinases; Laboratories; Mannosidase; Oncology, Experimental; Pharmacology, Experimental; Proteins; radiation resistance; Radiation therapy; Radiation Tolerance; Radiation, Ionizing; Radiotherapy; Stress response; Studies; Thapsigargin; Thyroid cancer; Thyroid carcinoma; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - radiotherapy; Tumor cell lines; Tumor cells; Tumors; Tunicamycin; United States > US; China
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2014.2956

Radiotherapy is one of the most effective forms of cancer treatment, used in the treatment of a number of malignant tumors. However, the resistance of tumor cells to ionizing radiation remains a major therapeutic problem and the critical mechanisms determining radiation resistance are poorly defined. In the present study, a cellular endoplasmic reticulum (ER) stress microenvironment was established through the pretreatment of cultured thyroid cancer cells with tunicamycin (TM) and thapsigargin (TG), in order to mimic the ER stress response in a tumor microenvironment. This microenviroment was confirmed through the X-box binding protein 1 splice process, glucose-regulated protein 78 kD and ER degradation-enhancing α-mannosidase-like mRNA expression. A clonogenic assay was used to measure cancer cell resistance to 60Co-γ following TM pretreatment; in addition, human C/EBP homologous protein (CHOP) mRNA expression was determined and apoptosis assays were performed. The results showed that TM or TG pretreatment inhibited CHOP expression and reduced the apoptotic rate of cells. Furthermore, the results demonstrated that the induced ER stress response rendered cancer cells more resistant to ionizing radiation-induced apoptosis. Therefore, the ER stress pathway may be a potential therapeutic target in order to improve the clinical efficiency of radiotherapy.