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

2004 ◽  
Vol 89 (3) ◽  
pp. 1108-1116 ◽  
Author(s):  
I. V. Scholz ◽  
N. Cengic ◽  
B. Göke ◽  
J. C. Morris ◽  
C. Spitzweg
Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3423-3432 ◽  
Author(s):  
C. Spitzweg ◽  
I. V. Scholz ◽  
E. R. Bergert ◽  
D. J. Tindall ◽  
C. Y. F. Young ◽  
...  

Abstract We reported recently the induction of androgen-dependent iodide uptake activity in the human prostatic adenocarcinoma cell line 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. In the current study, we examined the regulation of PSA promoter-directed NIS expression and therapeutic effectiveness of 131I in LNCaP cells by all-trans-retinoic acid (atRA). For this purpose, NIS mRNA and protein expression levels in the NIS-transfected LNCaP cell line NP-1 were examined by Northern and Western blot analysis following incubation with atRA (10 −9 to 10−6m) in the presence of 10−9m mibolerone (mib). In addition, NIS functional activity was measured by iodide uptake assay, and in vitro cytotoxicity of 131I was examined by in vitro clonogenic assay. Following incubation with atRA, NIS mRNA levels in NP-1 cells were stimulated 3-fold in a concentration-dependent manner, whereas NIS protein levels increased 2.3-fold and iodide accumulation was stimulated 1.45-fold. This stimulatory effect of atRA, which has been shown to be retinoic acid receptor mediated, was completely blocked by the pure androgen receptor antagonist casodex (10−6m), indicating that it is androgen receptor dependent. The selective killing effect of 131I in NP-1 cells was 50% in NP-1 cells incubated with 10−9m mib. This was increased to 90% in NP-1 cells treated with atRA (10−7m) plus 10−9m mib. In conclusion, treatment with atRA increases NIS expression levels and selective killing effect of 131I in prostate cancer cells stably expressing NIS under the control of the PSA promoter. Therefore atRA may be used to enhance the therapeutic response to radioiodine in prostate cancer cells following PSA promoter-directed NIS gene delivery.


2019 ◽  
Vol 23 (6) ◽  
pp. 1123-1130
Author(s):  
Emine Ecem ÇAKIR ◽  
Hasan ALHASAN ◽  
Elçin ÇAKIR ◽  
Ülkü ÇÖMELEKOĞLU

2020 ◽  
Author(s):  
Antonio J. León-González ◽  
Raúl M. Luque ◽  
Prudencio Sáez-Martínez ◽  
Juan M. Jiménez-Vacas ◽  
Vicente Herrero-Aguayo ◽  
...  

2018 ◽  
Vol 222 ◽  
pp. 133-147 ◽  
Author(s):  
Iván Arias-González ◽  
Alejandro M. García-Carrancá ◽  
Jorge Cornejo-Garrido ◽  
Cynthia Ordaz-Pichardo

2009 ◽  
Vol 285 (1) ◽  
pp. 58-65 ◽  
Author(s):  
Li Zhang ◽  
Jeffrey S. Davis ◽  
Stanislav Zelivianski ◽  
Fen-Fen Lin ◽  
Rachel Schutte ◽  
...  

2007 ◽  
Vol 5 (6) ◽  
pp. 631-640 ◽  
Author(s):  
Jacqueline Jonklaas

Normal thyrocytes and thyroid cancer cells are characterized by possession of a sodium iodide symporter. Radioiodine administration is a unique and powerful means of treating differentiated thyroid cancer because of the ability of thyroid cancer cells to concentrate beta-emitting radiolabeled iodine. Several manipulations, such as iodine depletion and thyroid hormone-stimulating hormone elevation, are used to enhance uptake of radiolabeled iodine by tumor cells. Adjuvant radioiodine therapy, given to patients without evidence of residual disease, enhances the sensitivity of subsequent surveillance and may decrease recurrence rates and mortality. However, its exact role in the management of low-risk patients merits further investigation. In contrast, radioactive iodine therapy used in patients with residual or metastatic disease clearly improves outcomes. Several studies show decreased recurrence and mortality rates in patients treated with radioiodine compared with those not receiving radioactive iodine. Adverse events from radioiodine therapy include salivary gland dysfunction, bone marrow suppression, and reproductive disturbances. Side effects of radioiodine therapy are generally greater when higher activities of radioiodine are used and may be transient or permanent. Secondary malignancies also may occur after radioiodine therapy. These side effects must be weighed against potential benefits, especially when radioactive iodine is used as adjuvant therapy. Stimulation of the expression of the sodium iodide symporter, or its introduction de novo into nonthyroid cells, is promising in treating poorly differentiated thyroid cancer and nonthyroid malignancies, respectively.


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