[Effect of soluble vascular endothelial growth factor (VEGF) receptor gene (sflt-1) and antisense VEGF nucleotide on neovascularization].
OBJECTIVE
Nutrients and growth factor provided by new blood vessel in tumor tissue is critical for fast growth of tumor, therefore, how to inhibit neovascularization and speedup neocrosis of tumor tissue is a promising way to treat tumor. This article emphasizes on both the blockage effect of soluble VEGF receptor gene (sflt-1) and antisense VEGF nucleotide on VEGF in tumor tissue, in order to inhibit its neovascularization.


METHODS
Effect of antisense VEGF on VEGF secretion in MM45T. Li cells was observed after infection with Ad-antisense VEGF; Effect of recombinant soluble VEGF receptor protein (3' delta Flt-1) on proliferation of (human umbilical vascular endothelial cell) HUVEC induced by VEGF was investigated; Effect of both antisense VEGF and sflt-1 on neovascularization were tested after Ad-anti VEGF or Ad-sflt-1 injected in chorion of chicken embryo.


RESULTS
VEGF concentration from infected MM45T. Li by recombinant Ad-antisense VEGF is only 15% of that from control group (P < 0.01); the proliferation of HUVEC induced by VEGF in condition medium containing 3' delta Flt-1 is significantly reduced, and negatively related with dose within certain range; Both sflt-1 and antisense VEGF nucleotide obviously inhibited formation of new blood vessel, even caused dead embryo.


CONCLUSIONS
Both sflt-1 and antisense VEGF could effectively inhibited neovascularization separately, combination therapy can enhance the inhibitory effect, but the mechanism is different.
Mi
Jun
J
Department of Biochemistry & Molecule Biology, Shanghai Second Medical University, Shanghai 200025, P. R. China.
Wang
Jian-hua
JH
Chen
Shi-shu
SS
D000256:Adenoviridae; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D002642:Chick Embryo; D004730:Endothelium, Vascular / Q000166:cytology; D015870:Gene Expression; D005822:Genetic Vectors; D006639:Histidine; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic; D016372:RNA, Antisense; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000302:isolation & purification; D012995:Solubility; D014407:Tumor Cells, Cultured; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000302:isolation & purification
D016372:RNA, Antisense; D011993:Recombinant Fusion Proteins; D006639:Histidine; D040281:Vascular Endothelial Growth Factor Receptor-1