<b>Conclusions:</b> These findings indicate that kaempferol suppresses the migratory and invasive abilities of PaCa cells by downregulating MMP-1 through negative regulation of the Akt and NF-κB signaling cascades, while kaempferol holds promise as a treatment strategy for GEM-R PaCa. Here, MMP1 is linked to permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome.