Sodium/iodide symporter gene transfection increases radionuclide uptake in human cisplatin-resistant lung cancer cells.

Abstract

The sodium/iodide symporter (NIS) is involved in iodide uptake and has been used for the diagnosis and treatment of thyroid cancer. Transfection of the NIS gene in A549 human lung cancer cells can induce radioactive iodine ((131)I) and radioactive technetium ((99m)Tc) uptake. The aim of the present study was to assess the role of NIS in (99m)Tc and (131)I uptake by the A549/DDP human cisplatin-resistant lung cancer cell line. To do so, recombinant adenovirus, adenovirus-enhanced green fluorescent protein-human NIS (Ad-eGFP-hNIS) and Ad-eGFP-rat NIS (Ad-eGFP-rNIS) vectors were established. These vectors were transfected into A549/DDP cells and xenograft tumors in nude mice. Assessment of (99m)Tc and (131)I uptake was performed. Results showed that the transfection efficiency of Ad-eGFP-hNIS and Ad-eGFP-rNIS in A549/DDP cells was at least 90 % in all experiments, and that the uptake ability of (99m)Tc and (131)I was highly enhanced (14-18 folds for (99m)Tc, and 12-16 folds for (131)I). However, the radionuclide concentration in transfected NIS genes' A549/DDP cells reached a plateau within 30-60 min, indicating that NIS transport led rapidly to (99m)Tc and (131)I saturation in cells. In xenograft tumor models, uptake of (99m)TcO4 (-) was obviously higher in the hNIS and rNIS groups compared with controls. In conclusion, these results support the hypothesis that A549/DDP cells can effectively uptake (99m)Tc and (131)I when transfected with the hNIS and rNIS gene. The rNIS or hNIS gene could be used as an effective method for the effective delivery of radioactive products to specific tissues for imagery and/or treatment.