Effects of aspirin on colon cancer using quantitative proteomic analysis.

Background: Colon cancer is one of the most prevalent digestive cancers worldwide. Results of epidemiological, experimental, and clinical studies suggest that aspirin inhibits the development of colon cancer. This study aimed to systematically elucidate the molecular mechanisms by which aspirin prevents colon carcinogenesis. Methods: We determined the global protein expression profiles of colorectal cancer and aspirin-treated cells using quantitative proteomic analysis. We analyzed the proteomic results using bioinformatics (including differential proteins, protein annotation, Kyoto Encyclopedia of Genes and Genomes [KEGG] pathways, and protein-protein interaction [PPI] network). The viability of the colon cancer cell line and HT29 ​cells treated with aspirin was determined using the cell counting kit-8 assay. The differentially expressed proteins, such as p53 and cyclin-dependent kinase 1 (CDK1), were quantified using real-time polymerase chain reaction (PCR) and Western blotting. We measured cell cycle distribution and apoptosis in HT29 ​cells exposed to aspirin using fluorescence-activated cell sorting (FACS). Results: We found that 552 proteins were significantly dysregulated, of which 208 and 334 were upregulated and downregulated, respectively, in colon cancer cells exposed to 10 ​mmol/L of aspirin (95% confidence interval [CI]: -1.269 to -0.106, Conclusions: These results indicate that aspirin induces G1 arrest and apoptosis in colorectal cancer cells via the p53-CDK1 pathway. Aspirin may be a promising drug candidate for colon cancer prevention.