CX-4945 has an antiproliferative effect on CCA and enhances the effect of gemcitabine and cisplatin through its inhibitory effect on the PI3K/AKT pathway and DNA repair.
We further identified the PI3K/AKT pathway as a dominant signal of Tip60 and suggested that Tip60 regulated CCA cell proliferation and metastasis via PT3K-AKT pathway.
Abnormal activation of the phosphatidylinositol 3-kinase (PI3K) pathway has been demonstrated in certain types of cancer, including cholangiocarcinoma (CCA).
Simultaneous activation of PI3K and Yap pathways frequently occurred in human liver tumor specimens and their combined suppression was highly detrimental for the growth of HCC and CCA cell lines.
The effects of human chorionic gonadotropin (hCG) and phosphoinositide 3 kinase (PI3K) on the expression and activation of PAK4 were investigated by treating CCA JEG3 and JAR cells with anti-hCG antibody and PI3K inhibitor, respectively.
PI3K pathway activation in hepato-biliary carcinomas was analyzed using immunohistochemistry for the downstream targets eIF4-E and phosphorylated 4E-BP1 on tissue microarrays. eIF4-E expression was found in 3/13 intrahepatic CCA (23%), 9/38 extrahepatic CCA (24%), 12/34 gallbladder carcinomas (35%), and 9/61 hepatocellular carcinomas (15%).