Effects of aurora kinase inhibitor on proliferation and apoptosis of breast cancer cells

Objective To investigate the effects of VX-680,a new aurora kinase inhibitor,on proliferation and apoptosis of MDA-MB-231 breast cancer cell lines.Methods MDA-MB-231 cells were cultured for 24 h in the medium which contained VX-680 with different concentrations.Inverted Microsoft showed cells varied with different concentrations.The effect of VX-680 on cell proliferation was examined by methyl thiazol tetrazolium (MTT) assay and colony assay.The cell cycle was analyzed by propidium iodide (PI) dyeing.The variety of nucleus and spindle morphology was tested by immunofluorescence.The levels of AuroraA/B protein,histone H3 and apoptosis relative protein expression were detected by Western blotting.Morphological changes of apoptotic cells were observed under the flurescent microscopy.Results VX-680 obviously inhibited the proliferation of MDA-MB-231 cells 24 h or 48 h after treatment,with the 50％ inhibitory concentration ( IC50 ) value being (2.362 ±0.599) μmol/L or (0.102 ±0.556) μnol/L.After treatment with VX-680,apoptosis of MDA-MB-231 cells was seen.The ratio of colony forming was decreased from (93.00 ±0.03)％ to (0.01 ±0.01 )％,the ratio of G0/G1 was decreased from (51.27 ±0.75)％ to (5.87 ±0.49)％,the percentage of G2/M cells was increased from (17.67 ± 1.25)％ to (91.93 ± 1.96)％,and the percentage of apoptotic cells was increased from (4.33 ±0.03)％ to (44.00 ±0.04 ) ％ ( P ＜ 0.05 ).The morphology of nucleus and spindle was abnormal.The expression levels of phosphorylated AuroraA/B and Histone H3 were significantly down-regulated,and the cleavage of PARP and Caspase-3 was detected by Western blotting.Conclusion VX-680 inhibited the proliferation and induced the apoptosis of MDA-MB-231 cells in a dose-dependent manner. Key words: Breast carcinoma;  VX-680 ;  Aurora;  Proliferation;  Apoptosis