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KMID : 0356620080230040238
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Journal of Korean Society of Endocrinology
2008 Volume.23 No. 4 p.238 ~ p.244
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Effects of Simvastatin on the Growth and Invasion of Anaplastic Thyroid Cancer Cells Lines
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Choi Hyun-Jeogn
Kim Tae-Yong
Kim Won-Bae
Kim Won-Gu
Shong Young-Kee
Kim Eui-Young
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Abstract
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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 ≥ 5 mM). Anchorage independent colony formation also decreased after
simvastatin (≥ 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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KEYWORD
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anaplastic thyroid cancer, chemotherapeutic agent, HMG-CoA reductase inhibitor
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