Abstract: The effects of Aspirin on tumor chemoprevention and inhibition have been debated and researched in recent years and its effects on colorectal cancer are quite clear. For breast cancer, however, conclusions are inconsistent and the anti-tumor mechanism of Aspirin is not clear yet. In our study, we used DMBA-induced mammary gland carcinogenesis model to assess the chemoprevention effect of Aspirin on mammary precancerous lesions. After SD rats were treated with Aspirin, the total numbers of precancerous lesion in experimental groups were 16 (40 mg/kg Aspirin) and 13 (20 mg/kg Aspirin), while the number in control group was 35. In vitro, we found that Aspirin inhibited cell proliferation in human breast cancer cell line MCF-7 by SRB assay with no apparent cytotoxity under the doses of 10, 8, 6, 4 and 2 mM, the inhibitory rates were 86.96%, 54.56%, 24.83%, 14.24% and 4.49%, respectively. In mechanism research, the results of gene microarray assay demonstrated that 4 mM and 2 mM Aspirin were effective in changing gene expression profile in MCF-7 cells. The expression of cell cycle regulator, cyclin A, was significantly down-regulated under the same doses, while the down-regulation of Cdk2 was only remarkable at 4 mM. Our findings reveal that Aspirin is effective in tumor inhibition during initial phase in rats. In MCF-7 cells, Aspirin reduces cell proliferation without significant cytotoxity and its possible mechanism involves altering tumor-related gene expression and regulating cell cycle process.

Key words: Aspirin, Non-steroidal anti-inflammatory drugs, Induced mammary gland carcinogenesis, Gene microarray, Cell cycle regulation