[17-AAG as radiation sensitizer]
>>J Clin Endocrinol Metab. 2006 Mar 14; [Epub ahead of print]
TREATMENT WITH DRUGS ABLE TO REDUCE IODINE EFFLUX SIGNIFICANTLY INCREASES THE INTRACELLULAR RETENTION TIME IN THYROID CANCER CELLS STABLY TRANSFECTED WITH SODIUM IODIDE SYMPORTER (NIS) cDNA.
Elisei R, Vivaldi A, Ciampi R, Faviana P, Basolo F, Santini F, Traino C, Pacini F, Pinchera A.
Department of Endocrinology and Metabolism, Section of Endocrinology, (R.E., A.V., R.C., F.S., A.P.); Department of Oncology, Division of Pathology III, (P.F., F.B.); Service of Radiation Safety, S. Chiara Hospital, (C.T.), University of Pisa, 56124 Pisa, Italy; Department of Internal Medicine, Endocrinolgy and Metabolism, and Biochemistry, University of Siena, 53100 Siena, Italy (F.P.); AMBISEN Center, High Technology Center for the Study of the Environmental Damage of the Endocrine and Nervous Systems, University of Pisa, 56100 Pisa, Italy (A.P.).
Context: one of the major limits of gene therapy with sodium iodide symporter (NIS), which enable cells to be subjected to radioiodine therapy, is that NIS transfected cells rapidly release the intracellular iodine. Methods: we transfected 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 the transfected clones with myricetin, lithium, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic-acid (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 4/9 TT clones were able to take up radioiodine and correctly expressed NIS protein on the plasma membrane. Kinetic analysis of iodide uptake in the two clones (FRO-19 and TT-2) with the highest uptaking activity revealed that the plateau was reached after 30 min by FRO-19 and 60 min by TT-2. The t1/2 of the iodide efflux was 9 min in FRO-19 and 20 min in TT-2. The treatment of the two cell lines with four different drugs revealed that DIDS and 17-AAG, but not myricetin and lithium, 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 NIS transfected thyroid tumoral cells, thus reinforcing the hope of using this approach for future clinical application, especially in patients with thyroid carcinoma no longer responsive to conventional therapy.<<
Full text freebie:
jcem.endojournals.org
Cheers, Tuck |
