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Original Article Effects of Simvastatin on the Growth and Invasion of Anaplastic Thyroid Cancer Cells Lines.
Hyun Jeung Choi, Tae Yong Kim, Eui Young Kim, Won Gu Kim, Won Bae Kim, Young Kee Shong
Endocrinology and Metabolism 2008;23(4):238-244
DOI: https://doi.org/10.3803/jkes.2008.23.4.238
Published online: August 1, 2008
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1Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Korea.
2Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Korea.

BACKGROUND
Anaplastic thyroid carcinoma has grave prognosis with most patient dying within 6 months of diagnosis. 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have been reported to have an anticancer effect in experimental and clinical studies. In this study, we investigated the effect of HMG-CoA reductase inhibitors on cell growth, invasiveness, adherence and signal transduction to evaluate the possibility of simvastatin as an agent for treatment of thyroid cancer. METHODS: The viability of simvastatin treated 3 thyroid cancer cell lines (FRO, WRO, and ARO) were determined. We evaluated the cell migration, anchorage-independent growth and invasion ability in anaplastic thyroid cell line. The expression and phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regurated kinase (ERK) were determined by immunoblot analysis. RESULTS: Three thyroid cancer cell lines showed concentration dependent decrease of viability after treatment with 100~200 mM of simvastatin. Anaplastic ARO cell line showed the most predominant decrease in viability. In ARO cell lines, cell migration was decreased by concentration dependent manner after treatment with simvastatin (concentration > or = 5 mM). Anchorage independent colony formation also decreased after simvastatin (> or = 10 mM). Finally, immunoblot analysis revealed that the phosphorylation status of FAK and ERK decreased in time dependent manner following treatment with 10 mM of simvastatin. CONCLUSION: The results of this study suggest that simvstatin exerts a favorable effect on the progression and metastasis of thyroid cancer. However, further studies are needed to elucidate the related mechanisms and signal transductions prior to its therapeutic application.

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