The results of both drugs on growth were virtually indistinguishable. Fluorescence activated BAY 11-7821 cell sorting analysis proved that treatment with either inhibitor caused G1 growth arrest and lack of cells in S phase, though no apoptosis was observed. Immunoblotting demonstrated that both drugs potently inhibited the phosphorylation of AKT on both activation sites, although the impact on S473 was stronger with MK2206. Both inhibitors also equally downregulated cyclin D3 expression, phosphorylation of PRAS40, an immediate target of AKT, and phosphorylation of the downstream translational regulators S6 and 4EBP1 on numerous sites while coordinately increasing p27 expression. In summary, inhibition of the AKT1 and AKT2 isoforms employing a particular, allosteric chemical was sufficient to induce a strong cell cycle arrest in PTEN mutant IGROV 1 cells. As treatment of mice bearing established IGROV 1 xenografts with either AKTi 1/2 or MK2206 had similar inhibitory RNApol effects on AKT phosphorylation and cyst growth, these were recapitulated in vivo. Taken together, our data suggest that in some ovarian cancers, AKT3 inhibition is dispensable for maximal antitumor activity and isoform selective inhibitors that spare AKT3 are sufficient to inhibit growth and signaling. To separate the roles of the AKT1 and AKT2 isoforms in mediating proliferation, IGROV 1 cells were treated with siRNA pools directed against AKT1, AKT2, or AKT3 alone or in combination. Transfection of cells with siAKT1 or siAKT2, although not the nontargeting control pool siRNA, led to successful down-regulation of expression of the respective AKT isoforms. We could not detect AKT3 knockdown in these cells, as they don’t express detectable quantities of AKT3 Aurora C inhibitor by immunoblot, and ergo see siAKT3 transfection in IGROV 1 as a control. Particular knockdown of AKT1, however not AKT2 or AKT3, was sufficient to induce substantial G1 arrest, loss in cells in S phase and downregulation of cyclin D3 expression and 4EBP1 phosphorylation and S6. Evidence of synergy was not observed following concomitant knockdown of multiple AKT isoforms, nor did apoptosis induced by combinatorial knockdown of more than one isoform. Over all, the results of AKT1 knock-down were just like those of the AKT 1/2 and pot AKT inhibitors, suggesting that AKT1 may be the main regulator of cell growth in IGROV 1 ovarian cancer cells. Synergistic effects of AKT and MEK inhibitors in PI3K and RAS triggered ovarian cancer cells Concurrent activation of the RAS and PI3K pathways does occur in an important percentage of human cancers and might need combined therapy to totally abrogate their co-operative effects on proliferation and cover dependent translation. Among the four cell lines with RAS/RAF process aberrations in our panel, the RAS mutant OVCAR 5 and KRAS zoomed SKOV 8 cells had high p AKT appearance, as well as elevated degrees of activated RAS.