Implication of biological function and regulatory mechanism of P2X7 purinergic receptor in Hepatocellular Carcinoma Cells

• Main Authors: Hsiao-Yun Chen, 陳筱昀
• Other Authors: 謝逸憲
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/29127843050097354785

碩士 === 中山醫學大學 === 生化暨生物科技研究所 === 103 === Human P2X7R (purinergic receptor P2X, ligand-gated ion channel-7), it belongs to the family of ATP ionotropic receptors. Known ATP activates P2X7R, apperance permeilization on the cell membrane, causing cells to apoptosis. Previous research indicated P2X7R is not conducive to a potential liver cancer prognosis. However, research has for P2X7R in human hepatocellular carcinoma (HCC) biological functions, signaling pathways and gene regulation mechanisms remain unclear. Firstly, Western blot analysis showed that P2X7R expression in hepatoma cells were higher than normal liver cells. The inhibitory effects of P2X7R on HCC cells growth were arrested in G0/G1 cell cycle, concomitant with a marked inhibition of SKP2 and cyclin D1 the induction of the p27 and p21. In addition, we demonstrated knockdown P2X7R decreased Akt activity-promoted migration and invasion, but also reduced KLK-10 and transcription factor MZF-1 expression. sh-P2X7R cells treatment with an Akt inhibitor LY294002 in HCC cells more significant inhibited the migration and invasion. Moreover, overexpression of Akt abolished P2X7R-mediated cell migration and invasion.P2X7R may be involved in malignant progression of HCC, and AKT is an important downstream signaling molecule that plays an essential role in mediating P2X7R induced cell proliferation, migration and invasion. On conclusion, P2X7R is a principal regulator of human HCC growth and may be a useful molecular target for HCC prognosis and treatment.