The purpose of this study was to determine the impact of sorafenib on PI3K/AKT/mTOR signaling pathway and to further define its mechanism for treating hepatocellular carcinoma (HCC).
We identified activation of Ras and downstream Ras effectors (ERK, AKT, and RAL) due to epigenetic silencing of inhibitors of the Ras pathway in all HCC.
These results support the hypothesis that AKT activation is a mechanism of HCV-induced hepatocarcinogenesis, suggesting that AKT can be a therapeutic target for the treatment of recurrent HCC subsequent to surgical resection.
Using siRNA mediated knockdown of AKT and STAT3, we suggested that the effects of IL-17 were operated through activation of the AKT signaling in HCC, which resulted in IL-6 production.
As the PI3K/AKT/mTOR signaling pathway is also activated abnormally in HCC, we evaluated the effect of sorafenib, in combination with a dual PI3K/mTOR inhibitor, BEZ235, on HCC cell proliferation and survival in vitro.
Taken together, these data suggest that MEG3 regulates the PTEN/AKT/MMP-2/MMP-9 signaling axis and contributes to HCC development by targeting miRNA-10a-5p.
Our study thus not only supports GALK1 and GALT as being possible novel targets for treating HCC, but also uncovers new post-transcriptional regulatory mechanisms that link the galactose metabolic pathway to protein expression of the PI3K/AKT pathway in hepatoma.
Cancer such as hepatocellular carcinoma (HCC) is characterized by complex perturbations in multiple signaling pathways, including the phosphoinositide-3-kinase (PI3K/AKT) pathways.
Expression of PTEN, p27, p21 and AKT mRNA and protein in human BEL-7402 hepatocarcinoma cells in transplanted tumors of nude mice treated with the tripeptide tyroservatide (YSV).
Thus, increased BZW2 expression in HCC can induce HCC progression and drug resistance via stimulating the PI3K/AKT/mTOR pathway, which may represent a new therapeutic target for HCC.
ODC1 promotes proliferation and mobility via the AKT/GSK3β/β-catenin pathway and modulation of acidotic microenvironment in human hepatocellular carcinoma.
After human HCC stem cells were treated with docetaxel, cell proliferation was assessed by methyl thiazolyl tetrazolium (MTT) method, the cell apoptotic rate was evaluated by flow cytometry, the expression of CD133 and sex determining region Y‑box 2 (SOX2) was determined by RT‑PCR and immunohistochemistry, and the protein levels of CD133, SOX2, phosphoinositide 3‑kinases (PI3K), AKT and phosphorylated AKT (p‑AKT) were analyzed by western blotting.