PI3K-AKT signaling facilitates tumor cell growth and inhibits apoptosis. Objective of this study was to investigate the role of AKT in gastrointestinal neuroendocrine tumor cells (GEP- NET) by using the specific AKT inhibitor triciribine. Furthermore, the role of PTEN, an inhibitory protein of AKT, was investitaged a possible predictor of sensitivity to AKT inhibitors. Crystal violet staining was used for the detection of cell number changes. Western blot analysis was performed for the expression of active, phosphorylated Akt (pAkt), total Akt, PTEN. RT-PCR as well as DNA- microarrays were used for analysis of gene expressions. Annexin V staining and DNA-Laddering were used for detection of apoptosis. Treatment with triciribine reduced tumor cell growth by up to 65% and dose-dependently decreased activated Akt (p-AKT) as well as the expression of cell cycle-promoting Cyclin-D1, an effector protein of AKT. mRNA amounts of the regulatory protein PTEN were small in treatment sensitive cell lines while they were high in nonresponding cell lines. Combination of triciribine with classic cytostatic drugs as well as with IGF-1R inhibitors led to synergistic antiproliferative effects. Conclusion: The PI3K-AKT pathway plays an important role for tumor cell growth of GEP- NETs. Sensitivity to inhibition of AKT was strongly correlated to baseline levels of activated AKT. PTEN expression was predictive for triciribine sensitivity in GEP-NET cells. Dual inhibition together with an IGF-1R inhibitor appears to be a promising approach to enhance effects of AKT inhibition in GEP-NET's and merits further elucidation.