nuclear factor-kappa b inhibition can enhance apoptosis of differentiated thyroid cancer cells induced by 131i核factor-kappa b分化型甲状腺癌的抑制细胞凋亡可以增强细胞诱导我到131年.pdfVIP

Nuclear Factor-Kappa B Inhibition Can Enhance Apoptosis of Differentiated Thyroid Cancer Cells Induced by 131I 1 . 1,2. 1 3 1 1 Zhaowei Meng * , Shanshan Lou , Jian Tan , Ke Xu , Qiang Jia , Wei Zheng 1 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China, 2 Tianjin Normal University, Tianjin, People’s Republic of China, 3 Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China Abstract Objective: To evaluate changes of nuclear factor-kappa B (NF-kB) during radioiodine 131 (131I) therapy and whether NF-kB inhibition could enhance 131I-induced apoptosis in differentiated thyroid cancer (DTC) cells in a synergistic manner. Methods: Three human DTC cell lines were used. NF-kB inhibition was achieved by using a NF-kB inhibitor (Bay 11-7082) or by p65 siRNA transfection. Methyl-thiazolyl-tetrazolium assay was performed for cell viability assessment. DNA-binding assay, luciferase reporter assay, and Western blot were adopted to determine function and expression changes of NF-kB. Then NF-kB regulated anti-apoptotic factors XIAP, cIAP1, and Bcl-xL were measured. Apoptosis was analyzed by Western blot for caspase 3 and PARP, and by flow cytometry as well. An iodide uptake assay was performed to determine whether NF-kB inhibition could influence radioactive iodide uptake. Results: The methyl-thiazolyl-tetrazolium assay showed significant decrease of viable cells by combination therapy than by mono-therapies. The DNA-binding assay and luciferase reporter assay showed enhanced NF-kB function and reporter gene activities due to 131I, yet significan