Anti-mitogenic effect of sorafenib and mefformin on human anaplastic thyroid carcinoma cells

Abstract

Objective To elucidate the effect of multi-kinase inhibitor sorafenib on anaplastic thyroid carcinoma cells in the presence or absence of metformin.Methods SW1736 and C643 cells were treated with sorafenib in the presence or absence of metformin for various periods of time.Cell viability was detected by MTT.Cell cycle and cell apoptosis were measured by flow cytometry.Caspase-3 activity was detected by colorimetric kit.Western blot was used to analyze pERK phosphorylation and cyclinD1 expression.Results Sorafenib inhibited the growth of anaplastic thyroid carcinoma cells and induced cell cycle arrest and cell apoptosis.The EC50 of sorafenib in SW1736 and C643 was 3.68 μmol/L and 4.87 μmol/L respectively.After sorafenib ± metformin treatment,the caspase3 activity was 131.5 ％ and 278.0％ (P＜0.01) in SW1736 cells,127.2％ and 196.6％ (P＜0.01) in C643 cells.On the molecular level,sorafenib inhibited the phosphorylation of ERK and decreased the expression of cyclinD1.Metformin amplified the growth inhibitory effect of sorafenib on anaplastic thyroid carcinoma cells.The cell viability was 0.76 ± 0.17 and 0.30 ± 0.04 (P＜0.01) in SW1736 cells,0.72 ± 0.09 and 0.34 ± 0.10 (P＜0.001) in C643 cells after 2.5 μmol/L sorafenib without or with 5 mmol/L metformin treatment.Conclusions The combination of sorafenib and metformin may be a potent strategy for the treatment of anaplastic thyroid carcinoma and other advanced cancers. Key words: Sorafenib ; Anaplastic thyroid carcinoma ; Growth inhibition ; Metformin