Sodium butyrate enhances the expression of baculovirus-mediated sodium/iodide symporter gene in A549 lung adenocarcinoma cells

Abstract

Increased expression of sodium/iodide symporter (NIS) is required for reporter gene imaging and effective radioiodine treatment of tumor. We investigated whether increased accumulation of iodine can be induced by sodium butyrate through a newly developed baculoviral transfer of the human NIS (hNIS) gene in A549 human lung adenocarcinoma. A recombinant baculovirus [Bac-cytomegalovirus (CMV)-hNIS] encoding hNIS gene under the control of the CMV promoter was constructed. After A549 cells were transfected with Bac-CMV-hNIS in the presence of sodium butyrate, the expression of hNIS protein was detected by immunofluorescence and western blot analysis. The uptake and efflux of iodine were determined after the incubation of the transfected cells with I-iodide in the presence or absence of sodium butyrate. Immunocytochemical staining and western blot analysis showed increased hNIS protein expression in A549 cells transfected with Bac-CMV-hNIS after sodium butyrate treatment. Bac-CMV-hNIS transfected A549 cells accumulated up to about nine times more I than nontransfected cells; the amount of I uptake increased in a sodium butyrate in dose-dependent manner (P<0.001). However, rapid efflux of radioactivity was observed, with 50% lost during the first 2 min after I-containing medium had been replaced by a nonradioactive medium. Our results indicated that an improved efficiency of baculovirus-mediated hNIS reporter gene imaging in lung adenocarcinoma is possible with treatment with sodium butyrate. However, additional conditions need to be defined to reduce the rapid efflux of radioiodine for the purpose of radionuclide therapy.