Oridonin effectively inhibited the phosphorylation of pan-AKT substrates and subsequently blocked downstream effector mTOR signaling in breast tumor cells with HER2 amplification/overexpression (SKBR3 and HCC1569), PTEN loss (MDAMB468, HMEC-shPTEN), mutant PI3K (HMEC-PIK3CAH1047R, mouse mammary epithelium with PIK3CAH1047R), and AKT1 overexpression (HMEC-myr-ATK1) (Figures 2 and 4), suggesting broad therapeutic benefits of Oridonin in breast cancer cells with hyperactivation of AKT signaling. The gene discussed is AKT1; the disease is breast carcinoma.