This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Scholz, I. V. Articles by Spitzweg, C. Search for Related Content PubMed PubMed Citation Articles by Scholz, I. V. Articles by Spitzweg, C.

Dexamethasone Enhances the Cytotoxic Effect of Radioiodine Therapy in Prostate Cancer Cells Expressing the Sodium Iodide Symporter

Department of Internal Medicine II (I.V.S., N.C., B.G., C.S.), Klinikum Grosshadern, Ludwig-Maximilians-University 81377 Munich, Germany; and Department of Endocrinology (J.C.M.), Mayo Clinic, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Christine Spitzweg, M.D., Klinikum Grosshadern, Medizinische Klinik II, Marchioninistrasse 15, 81377 Muenchen, Germany. E-mail: christine.spitzweg{at}med2.med.uni-muenchen.de.

Recently, we have reported the induction of prostate-specific radioiodine accumulation in prostate cancer cells (LNCaP) using a prostate-specific antigen (PSA)-promoter-directed expression of the sodium iodide symporter (NIS) gene. This offers the potential to treat prostate cancer with radioiodine.

The aim of our current study was to examine the regulation of PSA-promoter-directed NIS expression in NIS-transfected LNCaP cells (NP-1) by dexamethasone (Dex). For this purpose, NIS mRNA and protein expression levels were examined in NP-1 cells by Northern and Western blot analysis, respectively, after incubation with Dex (10^-8–10^-6 M) in the presence of 10^-9 M mibolerone. NIS functional activity was measured by iodide uptake assay. In addition, we examined regulation of in vitro cytotoxicity of 131-I by Dex in an in vitro clonogenic assay. After incubation with Dex, iodide accumulation in NP-1 cells increased up to 1.5-fold, whereas NIS mRNA and protein expression levels were increased up to 1.7-fold. This effect of Dex was blocked by the androgen receptor antagonist casodex (10^-6 M). The killing effect of 131-I in NP-1 cells was increased from 55% when incubated with mibolerone alone to 95% when treated with Dex (10^-7 M) plus mibolerone. Treatment of NP-1 cells with Dex resulted in an additional antiproliferative effect as measured by clonogenic assay and nonradioactive proliferation assay.

In conclusion, in addition to an antiproliferative effect, treatment with Dex increases androgen-dependent NIS mRNA and protein expression as well as iodide accumulation, resulting in an increased cytotoxic effect of 131-I in prostate cancer cells stably expressing NIS under the control of the PSA-promoter.

This work was supported, in part, by Grant Sp 581/3-1 (to C.S.) from the German Research Council (Deutsche Forschungsgemeinschaft, Bonn, Germany) and by the Mayo Foundation Prostate Cancer Specialized Program of Research Excellence Grant CA91956 (to J.C.M.).

Abbreviations: Dex, Dexamethasone; EGFP, enhanced green fluorescent protein; MEIA, microparticle enzyme immunoassay; NIS, sodium iodide symporter; PSA, prostate-specific antigen; SDS, sodium dodecyl sulfate.

This article has been cited by other articles:

				M. J. Willhauck, B.-R. Sharif Samani, F.-J. Gildehaus, I. Wolf, R. Senekowitsch-Schmidtke, H.-J. Stark, B. Goke, J. C. Morris, and C. Spitzweg Application of 188Rhenium as an Alternative Radionuclide for Treatment of Prostate Cancer after Tumor-Specific Sodium Iodide Symporter Gene Expression J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4451 - 4458. [Abstract] [Full Text] [PDF]

				S. Unterholzner, M. J. Willhauck, N. Cengic, M. Schutz, B. Goke, J. C. Morris, and C. Spitzweg Dexamethasone Stimulation of Retinoic Acid-Induced Sodium Iodide Symporter Expression and Cytotoxicity of 131-I in Breast Cancer Cells J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 69 - 78. [Abstract] [Full Text] [PDF]

				L. Bartalena, M. L Tanda, E. Piantanida, and A. Lai Glucocorticoids and outcome of radioactive iodine therapy for Graves' hyperthyroidism Eur. J. Endocrinol., July 1, 2005; 153(1): 13 - 14. [Full Text] [PDF]