The role of Akt activation in the response to chemotherapy in pancreatic cancer

The PI3K/Akt signaling pathway is constitutively activated in some pancreatic cancers; when activated, it inhibits chemotherapy-mediated apoptosis. We examined whether Akt activity correlates with apoptotic resistance to chemotherapy in pancreatic cancer.A panel of human pancreatic cancer cells was evaluated for basal Akt activity as well as response to three chemotherapies. Chemotherapy-induced cell death was evaluated following either up- or down-regulation of Akt activity. Evaluation of phosphorylation of p21Cip/Waf1, a downstream target of Akt, was also evaluated.There was a broad distribution among pancreatic cancer cell lines by Akt activity, as well as sensitivity to the three chemotherapeutic agents with no apparent correlation. Phosphorylation of p21Cip/Waf1, but not change in total levels, correlated with the chemosensitizing effect of Akt inhibition to paclitaxel.Basal Akt activity does not appear to be a useful predictor for selection of pancreatic cancers in targeting Akt to broadly induce chemosensitivity.