Expression of vascular endothelial growth factor and its role in oncogenesis of human gastric carcinoma

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 contai ning receptor (KDR) in human gastric cancer tissue were observed by immunoh istochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the comple te VEGF(165) complimentary DNA in either the sense or antisense orientation . The biological changes of the cells were observed in which VEGF was up-re gulated or downregulated. RESULTS VEGF-positive rate was 50%, and VEGF was mainly localized in the cy toplasm and membrane of the tumor cells, while KDR was mainly located in th e membrane of vascular endothelial cells in gastric cancer tissues and peri -cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells exp ressed KDR, localized in both the cytoplasm and membrane. Introduction of V EGF165 antisense into human gastric cancer cells (SGC-7901, immunofluoresce nce 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 VEGF(165) 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 xenograf ted tumor (at 33 days postimplantation, tomor volume. 345.40 +/- 136.31 mm( 3)) (P <0.05 vs control SGC-7901 group, 1534.40 +/- 362.88 mm(3)), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 d ays postimplantation, tomor volume: 2350.50 +/- 637.70 mm) (P <0.05 vs cont rol SGC-7901 group). CONCLUSION This study provides direct evidence that VEGF plays an. importan t role in the oncogenesis of human gastric cancer.