Endocrinol Metab > Volume 25(3); 2010 > Article
Endocrinology and Metabolism 2010;25(3):192-198.
DOI: https://doi.org/10.3803/EnM.2010.25.3.192    Published online September 1, 2010.
The Effect of Atorvastatin and Simvastatin on NIS Expression of the TPC-1 Cell under the Therapeutic Blood Concentrations.
Tae Kyoon Kim, Hye Sook Jung, Chang Shin Yoon, Jung Hae Ko, Hae Jung Jun, Min Jung Kwon, Sun Hee Lee, Mi Kyung Kim, Jeong Hyun Park
1Department of Internal Medicine, Pusan Paik Hospital, College of Medicine, Inje University, Busan, Korea. pjhdoc@chol.com
2Molecular Therapy Lab., Paik Memorial Institute for Clinical Research, Inje University, Busan, Korea.
3Department of Internal Medicine, Marynoll Medical Center, Busan, Korea.
Abstract
BACKGROUND
Although so many experimental trials have been done to improve the redifferentiation and responsiveness of radioiodide therapy, they have not yet yielded any satisfactory results. As statins inhibit both farnesylation and geranylgeranylation, they have been reported to have an antineoplastic and redifferentiation effect in experimental and clinical studies. In this study, we investigated the relationship between statins and the alteration of the NIS expression and, TPC-1 cell apotosis to evaluate the possibility of using statins as adjuvant therapeutic agents for papillary thyroid cancer. METHODS: We used the TPC-1 cell lines for our experiments. Cell viabilities were measured by CCK-8. The degrees of apoptosis and, the expressions of NIS mRNA and NIS protein were measured by flow cytometry, semi quantitative RT-PCR and Western blot assay. RESULTS: Increased levels of NIS mRNA and NIS protein were observed under therapeutic blood concentrations (concentrations of simvastatin: 20, 50, 80 nM, concentrations of atorvastatin: 50, 80,110 nM), but the dose-response relationship was only manifested within simvastatin. The TPC-1 cells showed a concentration dependent decrease of viability and an increase of apoptosis not under therapeutic blood concentrations, but under excessively high concentrations (after treatment with 10-50 microM of atorvastatin and with 1-10 microM of simvastatin). CONCLUSION: The results of this study show that effective therapeutic blood concentrations of simvastatin and atorvastatin can give a favorable effect on the NIS expression under effective therapeutic blood concentrations. Therefore, we demonstrated the possibility that simvastatin and atorvastatin might have an important role as adjuvant therapeutic agents to improve the responsiveness of radioiodide therapy for papillary thyroid cancer. Further studies are needed to clarify this issue.
Key Words: Thyroid Papillary Cancer, TPC-1 cell, Statin, NIS
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