The impotance of the IP3 kinase signaling pathway in hepatocellular carcinoma

HCC is the fifth of the most prevalent cancer types and it is not exactly curable. Phospho İnositol 3- Kinase (PI3K) pathway controls signaling pathways that play role in tumor formation and thus cell survival and proliferation. Including HCC, it is known that Akt (PKB) protein which is the mediator of this pathway becomes overactive in many cancer types. Molecular and cellular mechanisms of PI3K/Akt signaling pathway activation and inhibition in HCC cell lines have not been well established. The aim of the study is determinate the activity of PI3K/Akt signaling pathway and the molecular and cellular effect of inhibition this pathway. PI3K/Akt pathway activation and behavioral changes of the cells after inhibition of this pathway with LY294002 inhibitor; which is specific to PI3K; at basal and stimulated conditions in nine HCC cell lines were observed. Phoshorylated Akt in the protein level to identify activation of the pathway by using Western blotting and immunostaining methods were examined. For examine the changes of cells behavior; to determine cell proliferation MTT and BrdU incorporation assays, for cell mortality LDH test, for cell cycle analysis FACS analysis and for motility of the cells wound assay were used. That activation level of PI3K/Akt pathway is different levels in HCC cell lines and the activation of pathway is higher at poorly differentiated HCC cells than differentiated ones was determined. Beside it was observed that the PI3K/Akt pathway can stimulate with several growth factors. Cell proliferation decreases by inhibition of PI3K/Akt pathway; this decrease is a result of the G1 arrest in cell cycle and cell motility decrease were shown. The motility of cells increased with stimulation of this pathway and decreased with inhibition this pathway was observed. As a result, we found that, inhibition of PI3K/Akt pathway decreases cell proliferation and motility thus tumorogenic potential of cells. Our results indicate that, PI3K/Akt pathway is important in HCC and Akt pathway could be an important target in HCC treatment.