In the current research, to find the potential effects of PFD as a therapeutic strategy considering its pleiotropic features besides anti-fibrotic functions, we investigated the inhibitory effects of PFD and its combination with 5-FU on the TGF-β signaling pathway through in vitro and in vivo CRC models as a repurposing strategy. This evidence concerns the gene TGFB1 and colorectal carcinoma.