Influence of hepatic arterial blockage on blood perfusion and VEGF,MMP-1 expression of implanted lver cancer in rats  

作　　者：Wei-Jian Guo Jie Li Wan-Long Ling Wen-Hua Gu Jun-Yan Zhuang,Department of Oncology,Xinhua Hospital of Shanghai Second Medical University,Shanghai 200092,China Yong-Rui Bai,Department of Radiotherapy,Xinhua Hospital of Shanghai Second Medical University,Shanghai 200092,China Wen-Zhu Zhang Yu-Fan Cheng,Department of Pathology,Xinhua Hospital of Shanghai Second Medical University,Shanghai 200092,China 

出　　处：《World Journal of Gastroenterology》2002年第3期476-479,共4页世界胃肠病学杂志（英文版）

基　　金：Science and Technology Development Fund of Shanghai Municipality,No.004119086

摘　　要：AIM: To investigate the influence of hepatic arterial blockage on blood perfusion of transplanted cancer in rat liver and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1), and to explore the mechanisms involved in transarterial embolization (TAE)-induced metastasis of liver cancer preliminarily. METHODS: Walker 256 carcinosarcoma was transplanted into rat liver to establish the liver cancer model. Hepatic arterial ligation (HAL) was used to block the hepatic arterial blood supply and simulate TAE. Blood perfusion of tumor in control, laparotomy control, and HAL group was analyzed by Hoechst 33342 labeling assay, the serum VEGF level was assayed by ELISA, the expression of VEGF and MMP-1 mRNA was detected by in situ hybridization. RESULTS: Two days after HAL, the number of Hoechst 33342 labeled cells which represent the blood perfusion of tumor directly and hypoxia of tumor indirectly in HAL group decreased significantly compared with that in control group (329+/-29 vs 384+/-19, P【0.01). The serum VEGF level in the HAL group increased significantly as against that of the control group (93 ng.L(-1)+/-44 ng.L(-1) vs 55 ng.L(-1)+/-19 ng.L(-1), P【0.05). The expression of VEGF and MMP-1 mRNA in the tumor tissue of the HAL group increased significantly compared with that of the control and the laparotomy control groups (P【0.05). The blood perfusion data of the tumor, represented by the number of Hoechst 33342 labeled cells, showed a good linear inverse correlation with the serum VEGF level (r=-0.606, P【0.05) and the expression of VEGF mRNA in the tumor tissue ( r =-0.338, P【0.01). CONCLUSION: Blockage of hepatic arterial blood supply results in decreased blood perfusion and increased expression of metastasis-associated genes VEGF and MMP-1 of transplanted liver cancer in rats. Decreased blood perfusion and hypoxia may be the major cause of up-regulated expression of VEGF.AIM：To investigate the influence of hepatic arterial blodckage on blood perfusion of transplanted cancer in rat liver and the expression of vascular endothelial growth factor (VEGF)and matrix metalloproteinase-1(MMP-1),and to explore the mechanisms involved in transarterial embolization(TAE)-induced metastasis of liver cancer preliminarily.METHODS:Walker 256 carcinosarcoma was transplanted in to rat liver to establish the liver cancer model.Hepatic arterial ligation(HAL) was used to block the hepatic arterial blood supply and simulate TAE.Blood perfusion of tumor in control laparotomy control,and HAL group was analyzed by Hoechst 33342 labeling assay,the serum VEGF level was assayed by ELISA,the expression of VEGF and MMP-1 mRNA was detected by in situ hybridization.RESULTS:Two days after HAL.the number of Hoechst 33 342 labeled cells which represent the blood perfusion of tumor directly and hypoxia of tumor indirectliy in HAL group decreased significantly compared with that in control group (329±29VS 384±19,P<0.01),The serum VEGF level in the HAL group increased significantly as against that of the control group (93ng.L^-1±44ng.L^-1VS55ng.L^-1±19ng.L^-1,P<0.05),The expression of VEGFand MMP-1 mRNA in the tumor tissue of the HAL group increased significantly compared with that of the control and the laparotomy control groups(P<0.05),The blood perfusion data of the tumor represented by the number of Hoechst 33342 labeled cells,showed a good linear inverse correlation with the serum VEGF level(r=-0.606,P<0.05),and the expression of VEGF mRNA in the tumor tissue(r=-0.338,P<0.01).CONCLUSION:Blockage of hepatic arterial blood supply results in decreased blood perfusion and increased expression of metastasis-associated genes VEGF and MMP-1 of transplanted liver cancer in rats .Decreased blood Perfusion and hypoxia may be the major cause of upregulated expression of VEGF.

关 键 词：Animals Carcinoma 256  Walker Embolization  Therapeutic Endothelial Growth Factors Gene Expression Hepatic Artery Interstitial Collagenase LIGATION Liver Neoplasms  Experimental LYMPHOKINES Male RNA  Messenger RNA  Neoplasm RATS Rats  Wistar Research Support  Non-U.S. Gov't Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors 

分 类 号：R735.7[医药卫生—肿瘤]