Simvastatin Inhibits Cell Proliferation and Migration in Human Anaplastic Thyroid Cancer
AbstractMalignant human anaplastic thyroid cancer (ATC) is pertinacious to conventional therapies. The present study investigated the anti-cancer activity of simvastatin and its underlying regulatory mechanism in cultured ATC cells. Simvastatin (0–20 μM) concentration-dependently reduced cell viability and relative colony formation. Depletions of mevalonate (MEV) and geranylgeranyl pyrophosphate (GGpp) by simvastatin induced G1 arrest and increased apoptotic cell populations at the sub-G1 phase. Adding MEV and GGpp prevented the simvastatin-inhibited cell proliferation. Immunoblotting analysis illustrated that simvastatin diminished the activation of RhoA and Rac1 protein, and this effect was prevented by pre-treatment with MEV and GGpp. Simvastatin increased the levels of p21cip and p27kip proteins and reduced the levels of hyperphosphorylated-Rb, E2F1 and CCND1 proteins. Adding GGpp abolished the simvastatin-increased levels of p27kip protein, and the GGpp-caused effect was abolished by Skp2 inhibition. Introduction of Cyr61 siRNA into ATC cells prevented the epidermal growth factor (EGF)-enhanced cell migration. The EGF-induced increases of Cyr61 protein expression and cell migration were prevented by simvastatin. Taken together, these results suggest that simvastatin induced ATC proliferation inhibition through the deactivation of RhoA/Rac1 protein and overexpression of p21cip and p27kip, and migration inhibition through the abrogation of Cyr61 protein expression. View Full-Text
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Chen, M.-C.; Tsai, Y.-C.; Tseng, J.-H.; Liou, J.-J.; Horng, S.; Wen, H.-C.; Fan, Y.-C.; Zhong, W.-B.; Hsu, S.-P. Simvastatin Inhibits Cell Proliferation and Migration in Human Anaplastic Thyroid Cancer. Int. J. Mol. Sci. 2017, 18, 2690.
Chen M-C, Tsai Y-C, Tseng J-H, Liou J-J, Horng S, Wen H-C, Fan Y-C, Zhong W-B, Hsu S-P. Simvastatin Inhibits Cell Proliferation and Migration in Human Anaplastic Thyroid Cancer. International Journal of Molecular Sciences. 2017; 18(12):2690.Chicago/Turabian Style
Chen, Mei-Chieh; Tsai, Yuan-Chin; Tseng, Jen-Ho; Liou, Jr-Jiun; Horng, Steve; Wen, Heng-Ching; Fan, Yu-Ching; Zhong, Wen-Bin; Hsu, Sung-Po. 2017. "Simvastatin Inhibits Cell Proliferation and Migration in Human Anaplastic Thyroid Cancer." Int. J. Mol. Sci. 18, no. 12: 2690.
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