Abstract
While external ionizing radiation has been used for treating non-small cell lung cancer (NSCLC), improved efficacy of this modality would be an important advance. Ectopic expression of the sodium iodide symporter (NIS) and thyroperoxidase (TPO) genes in NSCLC cells facilitated concentration of iodide in NSCLC cells, which markedly induced apoptosis in vitro and in vivo. Pre-incubation of the NIS/TPO-modified NSCLC cells in iodide followed by ionizing radiation generates bystander tumoricidal effects and potently enhances tumor cell killing. This iodide-induced bystander effect is associated with enhanced gap junction intercellular communication (GJIC) activity and increased connexin-43 (Cx43) expression. Thus, iodide may serve as an enhancer to markedly improve the efficacy of radiation therapy in combined therapeutic modalities.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Apoptosis / drug effects
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Autoantigens / metabolism
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Autoantigens / pharmacology
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Bystander Effect
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Carcinoma, Non-Small-Cell Lung / genetics*
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Carcinoma, Non-Small-Cell Lung / metabolism
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Cell Death / drug effects
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Cell Death / radiation effects*
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Cell Line, Tumor
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Connexin 43 / metabolism
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Genetic Therapy
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Humans
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Iodide Peroxidase / metabolism
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Iodide Peroxidase / pharmacology
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Iodides / metabolism
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Iodides / pharmacology*
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Iron-Binding Proteins / metabolism
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Iron-Binding Proteins / pharmacology
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Lung Neoplasms / genetics
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Lung Neoplasms / metabolism*
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Radiation, Ionizing
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Sensitivity and Specificity
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Symporters / metabolism
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Transfection
Substances
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Autoantigens
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Connexin 43
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Iodides
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Iron-Binding Proteins
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Symporters
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sodium-iodide symporter
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TPO protein, human
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Iodide Peroxidase