Vascular endothelial growth factor promotes angiogenesis in gastric carcinoma

来源 :中国人民解放军军医大学学报 | 被引量 : 0次 | 上传用户:me272206010
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Objective: To explore the role of vascular endothelial growth factor (VEGF) in the angiogenesis and development of human gastric carcinoma. Methods: The expressions of VEGF and its receptor KDR (kinase-domain insert containing receptor) in human gastric cancer tissue and SGC-7901 cells were detected with immunohistochemical staining. Microvessel density (MVD) was obtained after immunostaining for FactorVIII. VEGF in SGC-7901 cell line was detected with West blot. VEGF levels were manipulated in human gastric cancer cell by using eukaryotic expression vector containing the complete VEGF165 complimentary DNA in either the sense or antisense orientation. Finally the biological characteristics of the transfectants were identified. Results: VEGF-positive rate in TNM grade Ⅲ and Ⅳ gastric carcinomas (19. 0%) were significantly higher than that in grade I and Ⅱ (72. 4%) (P<0. 05). Increased MVD was found in VEGF-positive tumors (16. 4± 6. 7), which is significantly larger than in VEGF-negative tumors (6. 5 ±- 2. 1) (P<0. 05). Human gastric cancer cells (SGC-7901) produced 3 kinds of VEGF in molecule. In 2 cases of 50 specimens, a few gastric cancer cells expressed KDR in cytoplasm and cell membranes. SGC-7901 ceils with antisense VEGF165 showed a significant reduction in cell surface VEGF protein with the immunofluorescence intensity from 8. 9% to 31.6% (P<0.05). However, those with stable integration of VEGF165 in the sense orientation resulted in an increase in cellular and cell surface VEGF with the immunofluorescence intensity from 75.4% to 31.6% (P<0. 05). The decrease of VEGF levels was associated with a marked decrease in the growth of nude mouse xenografted tumor (33 d post-implantation, 345.4±136.3 mm3 in size) (P<0. 05vs control SGC-7901 group), whereas VEGF overexpression resulted in an increase of xenografted tumor size(33 d post-implantation, 2 350. 5±637.7 mm3 in size) (P<0. 05 vs control SGC-7901 group). Conclusion:VEGF plays an important role in the development of human gastric cancer, and might have an autocrine effect upon the gastric cancer cells. The inhibition of VEGF by antisense RNA expression might prevent solid tumor from growing and metastasizing.
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