In conclusion, the combination of metformin and aspirin exert synergistic cytotoxicity in pancreatic cancer cell lines and significantly inhibitory effect on in vivo tumor growth by inducing apoptotic cell death through the downregulation of anti-apoptotic Bcl-2 family member Mcl-1 and Bcl-2, and the upregulation/activation of the pro-apoptotic BH3-only proteins Bim and Puma. This evidence concerns the gene BCL2 and familial pancreatic carcinoma.