To investigate the effects of Aurora kinase inhibitor AT9283 on the apoptosis, motility of basal-like breast cancer (BLBC) cells MDA-MB-231, and to explore the mechanism of AT9283 to reduce the invasion and metastasis of BLBC.

The different concentrations of AT9283 (0, 0.01, 0.1, 1, 10 μmol/L) were designed to deal with MDA-MB-231. Inhibitory rate of cell proliferation was detected by MTT. The variety of polyploid formulation was tested by flow cytometry with cells stained by propidium iodide (PI). Morphological change of apoptotic cells was analyzed by Yo-pro-1 staining. The apoptotic rate of MDA-MB-231 cells were determined by Annexin V/PI double-staining. The expression of apoptosis related proteins (Bcl-XL, Caspase-3 and PARP) and phosphorylation levels of Aurora kinase and Cofilin-1 were analyzed by Western blotting. The capability of motility was measured by wound-healing assay and chemotaxis assay.

After treatment of AT9283 (10 μmol/L) for 24 h, inhibitory rate of cell proliferation was (89.17±0.03)%. Fluorescence staining showed that the nuclei treated with AT9283 were stained green and the nuclei were fragmented. The formation of polyploid cells began at 48 hours after the addition of 1 μmol/LAT9283 to MD-MB-231 cells. AT9283 induced obviously the apoptosis of MDA-MB-231 cells (P<0.05), and the apoptotic rates were (13.4±2.5)%, (29.5±3.4)%, (52.8±6.7)%. Compared with (0.7±0.1)% of the control group, they were significantly increased (P<0.05). AT9283 effectively downregulated the expressions of Bcl-XL and promoted the dissection of Caspase-3 and PARP. The effect displayed obvious dose-effect relationship. AT9283 could significantly extend the healing time of scratches, decrease the migration cell count (P<0.05), and inhibit the phosphorylation of Aurora kinase and Cofilin-1 in a dose-dependent manner.

Aurora kinase inhibitor AT9283 can induce apoptosis and the motility of breast cancer cell line MDA-MB-231 through inhibiting phosphorylation of Aurora kinase and Cofilin-1.