Effect of simvastatin on the proliferation of human breast cancer cell MCF-7 and related mechanisms

SHEN Yuanyuan; DU Yingying; YUAN Yuan; PAN Yueyin

Abstract：Objective To observe the effect of simvastatin( SVA) on the proliferation of MCF?7 cells and elucidate its possi?ble molecular mechanisms. Methods MCF?7 cells were cultured in vitro. The inhibitory effects of different concenrations of SVA( 0, 3?25, 6?25, 12?5, 25, 50, 100μmol/L) on MCF?7 cells were measured by a tetrazolium?based colorimetric assay at 24, 48 and 72 h after treatment. The morphological changes of apoptosis induced by SVA( 0, 2, 4, 8 μmol/L) were observed by fluorescence staning under the fluorescence microscope. Cell cycles after treatment with SVA( 0, 4 μmol/L) were detected by flow cytometry. In addition, expression of intracellular Bcl?2 and Bax proteins were analyzed at 72 h after treatment with SVA(0, 2, 4, 8 μmol/L) by Western blotting. Results SVA inhibited proliferation of MCF?7 cells significantly in a dose? and time?dependent manner. Flow cytometry showed that the cell cycle was arrested at the G0/G1 phase after the treatment with SVA. Typical apoptotic morphologic changes were observed by fluorescence microscope, such as nuclear condensation and chromatin condensation. Analysis on expressions of intracellular Bcl?2 and Bax protein by Western blotting showed that, with the drug concentration increasing, the expressions of anti?apoptotic protein Bcl?2 were gradually suppressed but the expressions of apoptotic protein Bax were gradually increased. Conclusion SVA has the capa?bilities of inhibiting proliferation of MCF?7 cells in a dose?and time?dependent manner. Its cytotoxic effects seem to be of inducing cell cycle arrest and down?regulation of Bcl?2 and up?regulation of Bax.