In our study, the combination of AEE788, which is a dual receptor TKI of both EGFR and VEGFR, with the specific COX-2 inhibitor celecoxib not only demonstrated enhanced efficacy to inhibit colon cancer cell proliferation, migration and angiogenesis but also reduced colon CSCs subpopulation by targeting stemness-related pathways. Here, PTGS2 is linked to colonic neoplasm.