Abstract
The PI3K/Akt pathway is an attractive therapeutic target in the treatment of pancreatic cancer, as it was demonstrated to be aberrantly regulated in pancreatic cancer cells. The present study aimed to investigate the therapeutic potential of the novel Akt inhibitor MK-2206 in human pancreatic cancer cell lines. Pancreatic cancer cell survival following MK-2206 treatment was assessed using the Cell Counting Kit-8 (CCK-8) assay, colony formation and determination of the apoptotic rate by flow cytometry following annexin-V-fluorescein isothiocyanate/propidium iodide staining. The effects of MK-2206 alone or in combination with gemcitabine on pancreatic cell proliferation were assessed using the CCK-8 assay. Western blotting was used to examine the effects of the two drugs on Akt protein expression. The results demonstrated that MK-2206 inhibited the proliferation and induced apoptosis of the Mia PaCa-2 and Panc-1 pancreatic cancer cell lines. In addition, CCK-8 cytotoxicity test showed that combined administration of MK-2206 with gemcitabine enhanced the cytotoxic efficacy of gemcitabine. Furthermore, a low dose of MK-2206 (1 µM) combined with gemcitabine was enough to inhibit Akt phosphorylation. Taken together, these results provided some insight into the underlying mechanism of the anticancer effects of MK-2206 on pancreatic cancer cells.