Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor.
BACKGROUND
Radioactive iodine is used to identify and treat recurrent and metastatic thyroid cancer of follicular cell origin. Between 30% and 40% of thyroid cancers are either resistant or become resistant to radioactive iodine. Increased sodium-iodide symporter (NIS) and decreased Pendrin (PDS) activity may be associated with increased radioactive iodine effectiveness. In this investigation the effects of Trichostatin A (TSA), a histone deacetylating inhibitor, on human thyroid NIS and PDS gene expression was investigated.


METHODS
Cell lines from papillary, Hürthle, and follicular cell carcinomas were treated with TSA for 72 hours at concentrations up to 100 ng/mL. NIS and PDS gene expression was determined using quantitative RT-polymerase chain reaction.


RESULTS
. NIS messenger RNA expression in cell carcinomas was increased 107- (1.8-307) and 217- (5.7-408) fold in papillary, 39- (20-63) and 58- (37-80) fold in Hürthle, and 459- (178-810) and 781- (412-1229) fold in follicular after treatment with 50 and 100 ng/mL of TSA, respectively. PDS messenger RNA expression in cell carcinomas was decreased 0.22- (0.05-0.45) and 0.27- (0.09-0.47) fold in papillary, 0.53- (0.46-0.60) and 0.54- (0.44-0.64) fold in Hürthle, and 0.32- (0.26-0.39) and 0.56- (0.47-0.64) fold in follicular, after the same treatment.


CONCLUSIONS
In thyroid cancer cell lines, TSA dramatically increased NIS gene expression and reduced PDS expression. The increased NIS expression and reduced PDS expression may make radioiodine therapy more effective in patients with thyroid cancer, especially when the tumors have no or low uptake of radioiodine.
Zarnegar
Rasa
R
Department of Surgery, Division of General Surgery, and Cancer Center, University of California San Francisco/Mount Zion Medical Center, 1600 Divisadero Street, Room 437, San Francisco, CA 94143-1674, USA.
Brunaud
Laurent
L
Kanauchi
Hajima
H
Wong
Mariwil
M
Fung
Mami
M
Ginzinger
David
D
Duh
Quan-Yang
QY
Clark
Orlo H
OH
D002291:Carcinoma, Papillary; D002352:Carrier Proteins / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D026901:Membrane Transport Proteins; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D000076988:Sulfate Transporters; D027981:Symporters / Q000235:genetics; D013964:Thyroid Neoplasms; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology; D000099209:Sodium-Iodide Symporters
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007457:Iodine Radioisotopes; D026901:Membrane Transport Proteins; D019275:Radiopharmaceuticals; D000076988:Sulfate Transporters; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C085609:SLC26A4 protein, human; C012589:trichostatin A