Abstract:
To investigate the effects of ZM447439, a new Aurora kinase inhibitor, on the growth and cell cycle of T47D breast cancer cell lines in vitro. Methods: T47D was cultured in a medium for 24 h that contained different concentrations of ZM447439. Cell morphological changes were observed under an inverted microscope. The effects of ZM447439 on cell proliferation were examined via the mono-nuclear cell direct cytotoxicity assay and colony assay. The cell cycle of T47D cells was determined using flow cytometry. The levels of phosphorated AuroraA ( p-AuroraA ), total Aurora A ( T-Aurora A ), phosphorated Histone H3 ( p-Histone H3 ), total Histone H3 ( T-Histone H3 ), and CyclinB1 were determined using Western blot. Results: ZM447439 obviously inhibited the proliferation of T47D cells after 24, 48, or 72 h treatment in a dose- and time-dependent manner, with IC50 values of ( 9.604 ± 0.982 ) μmol/L, ( 3.413 ± 0.533 ) μmol/L, and (0.620±0.208) μmol/L, respectively. After treatment with ZM447439, apoptosis of the T47D cells occurred. Clonogenic assay was performed to elucidate the possible differences in the long-term effects of ZM447439 on human breast cells. The ratio of colony-forming was decreased from ( 93.00 ± 2.65 ) % to 0, the ratio of G0/G1 phase was decreased from ( 50.50 ± 1.71 ) % to ( 6.30 ± 0.17 ) %, that of S was decreased from ( 32.50 ± 2.70 ) % to 0, and the percentage of G2/M cells was increased from ( 17.00 ± 4.39 ) % to ( 93.70±0.17 ) % ( P < 0.05 ). Flow cytometry showed the G2/M arrest in a dose-dependent manner. ZM447439 inhibited p-AuroraA, p-Histone H3, and Cyclin B1. ZM447439 had no significant effect on the expression of T-Aurora A and T-Histone H3. Conclusion: ZM447439 may inhibit the growth of T47D cells and induce their G2/M arrest, indicating its potential as a new approach in treating breast cancer.