The Dynamic Changes Of Serum HIF-1a, VEGF, OPN, CTGF Levels With Treatment Of TACE Combined With Endostar In HCC Patients

Background&objectiveTACE is an operation by super selective inject into the target tumor arterial, pour into appropriate embolic agents to make arterial occlusion, then cause tumor necrosis. Now it has been the preferred method used as non operation treatment for patients with hepatocellular carcinoma. But TACE operation can cause hypoxia environment, which can induce angiogenesis and collateral circulation, restricted to many factors, only by TACE operation can not achieve the desired effects. Under hypoxia environment, expression of HIF-la raises.and then it can induce the VEGF, MMP, p53and PDGF-B elevation, especially VEGF, which can promote angiogenesis to meet the nutritional needs of tumor cells.OPN and CTGF can increase cell adhesion,migration and proliferation function,and induce tumor growth.OPN and CTGF are highly expressed in serum of hepatocellular carcinoma, and related to the outcome of tumor. Endostar have specific effects on vascular endothelial cells,inhibit their migration,induce apoptosis, directly bring to Anti-angiogenesis function. In this research we compared the changes of HIF-1α,VEGF,OPN,CTGF in serum of HCC patients with TACE and Endostar combined with TACE, then analysis the effect of Endostar combined with TACE on the invasion of liver cancer.Methods1Serum samples were taken from forty cases of HCC patients in Digestive System Department of Shan Dong provincial Hospital from July2012to february2013. They were all diagnosed by radiography,serology, medical Imaging or pathology methods. Twenty cases were treated with TACE alone as control group, Twenty cases of Endostar combined with TACE therapy as experimental group.2Test levels of HIF-1α,VEGF,OPN and CTGF by means of ELISA.3The measurement data is showed in (x±s) said, data is analysed by SPSS18statistical software. Comparison between groups data was performed using t test analysis, two variable correlation analysis was used to analysis correlation analysis.Results1.Serum levels of HIF-1α,VEGF,OPN,CTGF correlated significantly with two clinicopathological parameters, large tumor size and portal vein invasion;2.The level of HIF-1α,VEGF,OPN,CTGF before TACE operation have significant difference compared with3days after TACE and5days after TACE in both experimental and control group(p≤0.001),except the OPN(p=0.389) and CTGF (p=0.058)levels of5days after TACE in the control group. The level of HIF-1a, VEGF,OPN,CTGF5days after TACE operation have significant difference compared with3days after TACE in both experimental and control group(p<0.001).Compared to the control group,the increased VEGF level of3days after TACE and5days after TACE in experimental group has significant difference with VEGF level before TACE (p<0.05) While the increased HIF-1a,OPN and CTGF level of3days after TACE and5days after TACE have no significant difference (p>0.05),except the increased HIF-1α level of5days after TACE have significant difference (p=0.004) with the level of before TACE.3.Serum HIF-la level correlated positively with serum VEGF level(r=0.850,p<0.001),Serum HIF-la level correlated positively with serum CTGF level(r=0.800, p <0.001),Serum HIF-la level correlated positively with serum OPN level(r=0.796, p <0.001),Serum VEGF level correlated positively with serum OPN level(r=0.786, p <0.001),Serum VEGF level correlated positively with serum CTGF level(r=0.828, p <0.001),Serum CTGF level correlated positively with serum OPN level(r=0.778, p <0.001).Conclusions1Serum levels of HIF-lα,VEGF,OPN,CTGF correlated significantly with two clinicopathological parameters, large tumor size and portal vein invasion; while Serum HIF-lα level correlated positively with serum CTGF,VEGF and OPN, indicated that HIF-lα can up-regulate the expression of VEGF, OPN, CTGF levels.which indicates that serum levels of HIF-1α,VEGF,OPN,CTGF related to the invasiveness and growth of liver cancer2.3days of serum HIF-1α, VEGF, OPN, CTGF levels rapidly increased after operation than before operation, maybe related to the hypoxic environment caused by the embolization of tumor blood vessels.5days of serum HIF-1α, VEGF, OPN, CTGF levels decreased but still slightly higher than the preoperative levels, suggesting that TACE does not increase the tumor invasion in the treatment of disease at the same time.3Compared to the control group,the increased VEGF level of3days after TACE and5days after TACE in experimental group has significant difference with VEGF level before TACE, which can indicate that endostar have a certain role in the inhibition of angiogenesis.