The Research Of Glycolysis Of Hepatocellular Carcinoma To Growth And Proliferation

Background:Hepatocellular carcinoma(HCC) is one of common malignant tumor in our country, its incidence and mortality rates are rising., Tumor cell's main source of energy is sugar metabolism;Glucose in the body mainly by the glycolysis and oxidative phosphorylation two ways oxidative decomposition.Glycolytic pathway through the cell membrane of the glucose transporter(GLUT) glucose transport into the cell, to generate the pyruvic acid, a process known as "glycolysis.Pyruvic acid into lactic acid under anoxic conditions, and under aerobic conditions after metabolism of mitochondrial oxidative phosphorylation(OXPHOS) to produce energy.Cell activity state, closely related to cell energy gained by the rapid growth of malignant tumour, often appear dose of glucose in the cell to soar, glycolytic activity increase and the phenomenon of the lactic acid accumulation;Even under the condition of sufficient oxygen supply, glucose is still to lactic acid, the process called aerobic glycolysis of glucose metabolism or "Warburg effect", At present, the research on tumor associated with glucose metabolism, hepatocellular carcinoma and the relationship between glucose metabolism is no clear reports,This experiment by detecting cancer of the liver tissue and liver cancer cells, VEGF, HIF- 1 a GLUT- 1 expression and key enzymes in glycolysis pathway, and under the condition of hypoxia and oxygen, sugar liver cancer cell growth, further defined glycolysis in the role of liver cancer cell growth, invasion, and its relationship with angiogenesis in tumor microenvironment, the liver glucose uptake and utilization in order to have a more clear understanding, can put forward by inhibiting hepatocellular carcinoma on glucose utilization and the key enzymes of glycolysis pathway to achieve the purpose of inhibiting growth and metastasis of liver cancer, looking for new therapeutic targets for advanced liver cancer to provide theoretical and experimental basis.Objective: Hope that through the ressarch to verify whether hepatocellular carcinoma mainly through glycolytic pathway to obtain energy, the liver glucose uptake and utilization in order to have a more clear understanding, can inhibit cancer of the liver to glucose utilization and the key enzymes of glycolysis pathway to cut off the power source, achieve the purpose of inhibiting growth and metastasis of liver cancer, looking for new therapeutic targets for advanced liver cancer to provide theoretical and experimental basis.Methods: By immunohistochemical method to detect hepatocellular carcinoma tissue and normal liver tissues GIUT- 1, the expression of VEGF and HIF- 1 a;Rt-pcr detect pyruvate kinase PK, hexokinase HK, lactate dehydrogenase(LDH expressed in liver cancer and normal liver tissue;Hepatocellular carcinoma(HCC) hypoxia model is set up, make liver cancer cells in hypoxia, often oxygen and under the condition of low sugar, low sugar, hypoxia training by Western Blot detection, GIUT- 1 HIF-1 a express, and compare the cell growth inhibition rate between groups.Results: This study found that the in hepatocellular carcinoma tissue, GLUT-1, HIF- 1 a, VEGF protein expression is significantly higher than the normal liver tissue, and the difference has statistical significance(P < 0.05).This experiment by RT-PCR methods found in HK, pyruvate kinase PK, hexokinase three key enzyme lactate dehydrogenase(LDH m RNA expression levels were significantly higher than those of normal liver tissue, statistically significant difference(P < 0.05).Hepatocellular carcinomar cells respectively under the condition of oxygen and oxygen often develop 24 h, found no difference between the two groups of liver cancer cell growth inhibition rate(P > 0.05), by Western Blot experiments testing GLUT- 1expression in two groups of cells, the results showed that hypoxia did not affect liver cancer cells to use the uptake of glucose and no obvious difference between the two groups(P > 0.05).However, when the liver cancer cells under the condition of(oxygen + sugar) develop liver cancer cells after 24 h of HIF- 1 a protein expression significantly lowered, the growth of liver cancer cells was significantly inhibited(P < 0.05).Conclusions: Through this study result shows that GLUT- 1, HIF- 1 a, VEGF protein expression in Hepatocellular carcinoma group is high, may with liver cancer cells malignant transformation, growth, there exists a close relationship.And cancer of the liver tissue of HK, PK, LDH m RNA expression level obviously higher than that of normal liver tissue, further confirmed that the liver cancer cells through the glycolytic pathway as the main production way, provides the main energy source for liver cancer cell growth, invasion.Related proteins and key enzymes are providing a new method that can be used as a target for the treatment of liver cancer.