In line with our expectations, the results suggested that the significantly down-regulated PI3K/Akt, RAF/MEK/ERK, and NF-κB/COX-2/PGE2 signaling pathway were indeed to be responsible for the synergistic inhibition of colon cancer cell growth mediated by Aspirin combined with Cisplatin, as Aspirin combined with Cisplatin treatment caused more serious blockade of any of these three pathways compared to Aspirin treatment alone. This evidence concerns the gene PTGS2 and malignant colon neoplasm.