In the present study, we investigated whether AKT2 silencing sensitized pancreatic cancer L3.6pl, BxPC-3, PANC-1 and MIAPaCa-2 cells to gemcitabine via regulating PUMA (p53-upregulated modulator of apoptosis) and nuclear factor (NF)-κB signaling pathway. Here, TP53 is linked to pancreatic neoplasm.