Zheng Lu, Gong Wei, Liang Ping, Huang XiaoBing, You Nan, Han Ke Qiang, Li Yu Ming, Li Jing
Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Xin Qiao Main Street, Chongqing, 400037, China.
Tumour Biol. 2014 May;35(5):4095-9. doi: 10.1007/s13277-013-1535-z. Epub 2014 Jan 15.
This study aims to investigate effects of alpha-fetoprotein (AFP)-activated phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway on hepatocellular carcinoma cell proliferation. Active cirrhosis patients after hepatitis B infection (n = 20) and viral hepatitis patients with hepatocellular carcinoma (HCC) (n = 20) were selected as the subjects of the present study. Another 20 healthy subjects were selected as the control group. The serum AFP expression and liver tissue PI3K and Akt gene mRNA expression were detected. The hepatoma cell model HepG2 which had a stable expression of AFP gene was used. Real-time quantitative PCR and Western blot and other methods were used to analyze the intracellular PI3K and Akt protein levels. Compared with control group and cirrhosis group, the serum AFP levels in HCC group significantly increased, and the tissue PI3K and Akt mRNA expression also significantly increased. HepG2 cells were intervened using AFP, in which the PIK and Akt protein expression significantly increased. After intervention by use of AFP monoclonal antibodies or LY294002 inhibitor, the PIK and Akt protein expression in HepG2 cell was significantly decreased (P < 0.05). AFP can promote the proliferation of hepatoma cells via activation of PI3K/Akt signaling pathway.
本研究旨在探讨甲胎蛋白(AFP)激活的磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路对肝癌细胞增殖的影响。选取乙型肝炎感染后活动性肝硬化患者(n = 20)和病毒性肝炎合并肝癌(HCC)患者(n = 20)作为本研究对象。另选20名健康受试者作为对照组。检测血清AFP表达及肝组织PI3K和Akt基因mRNA表达。采用AFP基因稳定表达的肝癌细胞模型HepG2。运用实时定量PCR和蛋白质免疫印迹等方法分析细胞内PI3K和Akt蛋白水平。与对照组和肝硬化组相比,HCC组血清AFP水平显著升高,组织PI3K和Akt mRNA表达也显著升高。用AFP干预HepG2细胞后,PIK和Akt蛋白表达显著增加。采用AFP单克隆抗体或LY294002抑制剂干预后,HepG2细胞中PIK和Akt蛋白表达显著降低(P < 0.05)。AFP可通过激活PI3K/Akt信号通路促进肝癌细胞增殖。