Downregulation of Akt1 inhibits anchorage-independent cell growth and induces apoptosis in cancer cells

The serine/threonine kinases, Akt1/PKB alpha, Akt2/PKB beta, and Akt3/PKB-g amma, play a critical role in preventing cancer cells from undergoing apopt osis. However, the function of individual Akt isoforms in the tumorigenicit y of cancer cells is still not well defined. In the current study, we used an Akt1 antisense oligonucleotide (AS) to specifically downregulate Akt1 pr otein in both cancer and normal cells. Our data indicate that Akt1 AS treat ment inhibits the ability of MiaPaCa-2, H460, HCT-15, and HT1080 cells to g row in soft agar. The treatment also induces apoptosis in these cancer cell s as demonstrated by FACS analysis and a caspase activity assay. Conversely , Akt1 AS treatment has little effect on the cell growth and survival of no rmal human cells including normal human fibroblast (NHF), fibroblast from m uscle (FBM), and mammary gland epithelial 184B5 cells. In addition, Akt1 AS specifically sensitizes cancer cells to typical chemotherapeutic agents. T hus, Akt1 is indispensable for maintaining the tumorigenicity of cancer cel ls. Inhibition of Akt1 may provide a powerful sensitization agent for chemo therapy specifically in cancer cells.