Specific protein kinase C makes tight junctional differences between pancreatic cancer cells and normal pancreatic duct epithelial cells

s / Pancreatology 13 (2013) S1–S80 S17 down-regulation of Bcl-2 or Bcl-xL protein expression had a much weaker effect on PaCa apoptosis. Surprisingly, simultaneous knock-down of BclxL and Mcl-1 induced apoptosis strongly. However, simultaneous knockdown of Bcl-xL and Bcl-2 or Mcl-1 and Bcl-2 had no additive effect. The apoptosis inducing effect of simultaneous knock-down of Bcl-xL and Mcl1 is associated with Bax activation, mitochondrial cytochrome c release, and caspase cascade. Furthermore, the apoptosis-inducing effect of simultaneous knock-down of Bcl-xL and Mcl-1 was confirmed in animal model. Conclusions: These data suggest Bcl-xL and Mcl-1 as a potential therapeutic target for PaCa treatment and may help to develop novel therapeutic strategies for PaCa cells.