In this context, our objective is to evaluate the influence of Abemaciclib as a selective CDK4/6 inhibitor and Celecoxib as a selective Cox-2 inhibitor, as well as their combination, on the autophagic machinery in HCT-116 and Caco-2 CRC cell lines via measuring the expression levels of LC3, Beclin-1, ATG5, and p62. Here, ATG5 is linked to colorectal carcinoma.