Original Research
Copyright ©The Author(s) 2001. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 15, 2001; 7(4): 500-505
Published online Aug 15, 2001. doi: 10.3748/wjg.v7.i4.500
Expression of vascular endothelial growth factor and its role in oncogenesis of human gastric carcinoma
Du-Hu Liu, Xue-Yong Zhang, Dai-Ming Fan, Yu-Xin Huang, Jin-Shan Zhang, Wei-Quan Huang, Yuan-Qiang Zhang, Qing-Sheng Huang, Wen-Yu Ma, Yu-Bo Chai, Ming Jin
Du-Hu Liu, Xue-Yong Zhang, Dai-Ming Fan, Institute of Digestive Disease, Xijing Hospital, Xi’an 710033, Shaanxi Province, China
Yu-Xin Huang, Department of Gastroenterology, Tangdu Hospital, Xi’an 710033, Shaanxi Province, China
Jin-Shan Zhang, Wei-Quan Huang, Yuan-Qiang Zhang, Department of Histology and Embryology, Xi’an 710033, Shaanxi Province, China
Qing-Sheng Huang, Wen-Yu Ma, Department of Microbiology, Xi’an 710033, Shaanxi Province, China
Yu-Bo Chai, Ming Jin, Department of Biochemistry, Fourth Military Medical University, Xi’an 710033, Shaanxi Province, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Du-Hu Liu, Institute of Combined Injury, Third Military Medical University, Chongqing 400038, China. liuduhu@163.net
Telephone: 0086-23-68752000 Ext.71554(O), 68753270(H)
Received: January 6, 2001
Revised: January 8, 2001
Accepted: January 15, 2001
Published online: August 15, 2001
Abstract

AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly.

METHODS: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF165 complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated.

RESULTS: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF165 antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein ( immunofluorescence intensity, 8.9%) (P < 0.05). Conversely, stable integration of VEGF165 in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P < 0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 d postimplantation, tomor volume: 345.40 ± 136.31 mm3) (P < 0.05 vs control SGC-7901 group: 1534.40 ± 362.88 mm3), whereas up regulation of VEGF resulted in increased xenografted tumor size (at 33 d postimplantation, tomor volume: 2350.50 ± 637.70 mm3) (P < 0.05 vs control SGC-7901 group).

CONCLUSION: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.

Keywords: endothelial growth factor/analysis; angiogenesis; solid tumor; stomach neoplasms/pathology; endothelium; vascular