Background: One of the major limits of gene therapy with sodium iodide symporter (NIS), which enables cells to be subjected to radioiodine therapy, is that NIS transfected cells rapidly release the intracellular iodine.
Materials and methods: We transfected two human anaplastic (FRO) and medullary (TT) thyroid cancer derived cell lines, unable to take up iodine, with human NIS cDNA. The possibility of increasing the iodine retention time by treating cells with myricetin, lithium, 17-AAG and DIDS was explored.
Results: We obtained 19 FRO and 16 TT clones stably transfected with NIS; 12/19 FRO and 9/16 TT clones expressed the full length NIS mRNA; 11/12 FRO and 2/9 TT clones were able to specifically take up radioiodine and correctly expressed NIS protein on the plasma membrane. Kinetic analysis of iodide uptake in the two clones with the highest uptaking (FRO-19 and TT-2) activity revealed that the plateau was reached after 30 minutes by FRO-19 and 60 minutes by TT-2. The t1/2 of the iodide efflux was 9 minutes in FRO-19 and 20 minutes in TT-2. The treatment of the two cell lines with four different drugs revealed that DIDS and 17-AAG significantly increased the intracellular iodide retention time in FRO-19, but not in TT-2.
Conclusions: We showed that 17-AAG and DIDS prolong the retention time of 131-I in thyroid tumoral cells transfected with NIS, thus increasing the possibility of using efficiently this approach for future clinical application, especially in those patients with dedifferentiated thyroid carcinoma no longer responsive to conventional therapy.
01 - 05 Apr 2006
European Society of Endocrinology