Since PI3K/Akt can down-regulate p27Kip1 expression via phosphorylation and inhibition of FoxO transcription factors, (the known inducers of p27Kip1 transcription) [36], and TRG treatment in serum-containing media results in increased FoxO1Thr24/FoxO3aThr32 phosphorylation (Figure 5B), it is conceivable that TRG utilizes this mechanism to decrease p27Kip1 expression in HCC cells. This evidence concerns the gene AKT1 and hepatocellular carcinoma.