Effects Of AKT Inhibitor MK2206 On Proliferation And Apoptosis Of Breast Cancer Cells

Objective:To study the effects of Akt inhibitor MK2206 on the proliferation and apoptosis of human breast cancer cell lines T47D and MDA-MB-231,and to elucidate the possible mechanism of such effects.Methods:Human breast cancer T47D and MDA-MB-231 cell lines were cultured in vitro and treated with different concentrations of MK2206,respectively.Inhibitory effect of MK2206 on cell proliferation was examined by MTT assay.The apoptosis rates of T47D and MDA-MB-231 cells induced by MK2206 were detected by flow cytometry(FCM).The expression levels of caspase-3,poly(ADP-ribose)polymerase(PARP),bcl-2,bax,phosphorate-AKT(p-AKT)and total Akt(T-Akt)proteins were detected by Western blotting.Results:1.The proliferation of T47D and MDA-MB-231 cells were inhibited after treatment with MK2206 at 0.1,15 10 and 100 nmol/L for 24 h,respectively.The effect of the dose dependent was observed by the MTT analysis in the two cell lines.The IC50 of T47D and MDA-MB-231 cells were(5.139±0.711)and(18.380±1.264)nmol/L.2.The Annexin V/PI showed that the apoptosis rates of T47D and MDA-MB-231 cells were dose-dependented increased induced by MK2206.3.In the two cell lines,Western blot showed that the expression levels of caspase-3,PARP and bax proteins were up-regulated,while the expression levels of bcl-2 and p-Akt proteins were down-regulated.All of these effects occurred in a dose-dependent manner.MK2206 had no significant effect on the expression of T-Akt.Conclusions:MK2206 can inhibit the proliferation and induce the apoptosis in human breast cancer cell lines T47D and MDA-MB-231.These effects may be related with the down-regulation of p-AKT and the inhibition of PI3K-Akt signaling pathway.