Hepatocyte Nuclear Factor 4α Inhibit The Proliferation, The Invasiveness And The Expression Of New Angiogenesis Related Genes In Rat Hepatocellular Carcinoma Cells

Hepatocellular carcinoma (HCC) is one of the most common malignant gastrointestinal tumors in our country. The illness progress of HCC is very fast and the treatment effect is very poor. The 5 years of survival rate at about 7% on average. At present, one of the most effective treatment methods is still surgical treatment. But, the high rate of relapse for postoperative mortality in patients with liver cancer is seriously affecting the effects of surgical treatment. Researchers hope that through the mechanism of metastasis and recurrence of hepatocellular carcinoma (HCC) research to seek effective treatment strategies to control postoperative metastasis and recurrence of hepatocellular carcinoma (HCC). But after nearly 30 years, although the study have found that some abnormal genes associated with hepatocellular carcinoma metastasis and recurrence, but the control effect is not good.The structure of Hepatocyte nuclear factor-4a is a zinc finger protein and its amino acid sequence is highly conserved during evolution. In recent years, the study have found that the expression of HNF-4 alpha volume is down in the process of primary liver cancer. Studies have shown that Hepatocyte nuclear factor-4a is indispensable for maintaining ideological function of liver cells and differentiation. Hepatocyte nuclear factor-4α is one of control gene for normal liver cells epithelial phenotype. The research have proved that Hepatocyte nuclear factor-4a control the gene of normal liver cells is over 42%. Yin and other scholars studies have reveals that Hepatocyte nuclear factor-4a prevent the development mechanism of hepatocellular carcinoma (HCC) through cut Wnt/beta-catenin activity of cell signaling pathways. The Wnt/beta-catenin cell signaling pathway plays a regulation in many tissue proliferation, differentiation and migration, its also plays an important role in the liver cells. Studies have shown that the process of tumor growth and metastasis, requires the participation of new blood vessels. VEGF and Ang-2 are the main angiogenic factors. Studies have confirmed that the BNL liver cancer cells which high expression of VEGF and Ang-2 genes injected into mice, found that tumor growth significantly faster than the pure high expression of VEGF and simple high expression Ang-2 groups. Upside down, given VEGF monoclonal antibody and Ang-2 monoclonal antibody in models which have injected tumor cells into mice. The experimental results show that the effect of at the same time give two antibody inhibit tumor growth is better than use a single monoclonal antibody. In our study, CBRH-7919 cells were transfected with adenovirus vector.CBRH-7919 cell viability was detected by cell counting kit-8 (CCK8) assay and the migration and invasion were assessed by Transwell assays. The expression of Ang-2S VEGF were detected by RT-PCR and Western-blotting. In vivo study, a total of 12 rat were randomly divided into 3 groups (n=4 for each group):CBRH-7919group, CBRH-7919-Null-Vector group and CBRH-7919-HNF4a group, and received an injection of CBRH-7919 cells,CBRH-7919-Null-Vector cellsand CBRH-7919-HNF4acells(1×107/ml), respectively via the rest of liver after the establishment of subtotal hepatectomy model (70%).4 weeks later, the expression of Ang-2、VEGFin the liver tissues were detected by immunohistochemical assay, and were compared among 3 groups. We found that Hepatocyte nuclear factor-4a can significantly inhibit proliferation and metastasis capability of CBRH-7919,as well as inhibits the expression of Ang-2、VEGF in CBRH-7919. This study could be a new treatment for primary liver cancer, provides new ideas in the future scientific research and clinical research.