In the present study, treatment of A549 adenocarcinoma cells with a differentiation medium containing IBMX, Dexamethasone, Insulin and rosiglitazone resulted in a severe phenotypical change and the near‐ablation of features such as proliferation, migration, clonogenicity and 3D spheroid formation, indicative of aggressiveness. Here, INS is linked to adenocarcinoma.