Iodide sensitizes genetically modified non-small cell lung cancer cells to ionizing radiation.
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.
Zhang
L
L
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA and Veterans Affairs Greater Los Angeles Healthcare System, CA 90095, USA.
Sharma
S
S
Hershman
J M
JM
Brent
G A
GA
Dubinett
S M
SM
Huang
M
M
D017209:Apoptosis / Q000187:drug effects; D001324:Autoantigens / Q000378:metabolism / Q000494:pharmacology; D024201:Bystander Effect; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects*; D045744:Cell Line, Tumor; D018031:Connexin 43 / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism / Q000494:pharmacology*; D033862:Iron-Binding Proteins / Q000378:metabolism / Q000494:pharmacology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing; D012680:Sensitivity and Specificity; D027981:Symporters / Q000378:metabolism; D014162:Transfection; D000099209:Sodium-Iodide Symporters
D001324:Autoantigens; D018031:Connexin 43; D007453:Iodide Peroxidase; D007454:Iodides; D033862:Iron-Binding Proteins; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C056658:TPO protein, human