[Regulatory effect of antisense VEGF121 cDNA transfection on angiogenesis and metastasis of human lung giant cell carcinoma].
OBJECTIVE
To study the regulatory effect of antisense VEGF121 cDNA transfection on endogenous VEGF secretion and angiogenesis of human metastatic lung carcinoma cell line PG and explore the significance of microvessel density (MVD) in tumor growth and metastasis.


METHODS
The eukaryotic expression vectors bearing antisense VEGF121 cDNA was transfected into PG cells. Human umbilical vein endothelial cells (HUVEC) were cultured in conditioned mediums from transfected cells, and proliferation was determined by methyl thiazolyl tetrazolium (MTT) and 3H thymidine incorporation (3H TdR) assays in vitro. Microvessel density (MVD) in xenografted tumors in nude mice was analyzed by immunohistochemistry.


RESULTS
The transfectant of antisense VEGF121 cDNA exhibited a reduction in VEGF secretion. HUVEC grown in conditioned medium from the antisense VEGF transfected cells exhibited a decrease in capacities of DNA syntheses and cell proliferation. MVD of tumor with transfected antisense VEGF gene was significantly lower than that in control vector.


CONCLUSIONS
Antisense VEGF gene transfection can inhibit vascular endothelial cell proliferation in vitro and tumor angiogenesis in vivo, which may explain its inhibitory effects on tumor growth and metastasis.
Department of Pathology, Peking University, Beijing 100083, China.
X
X
Wu
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J
Zheng
J
J
Fu
D000818:Animals; D016375:Antisense Elements (Genetics); D018286:Carcinoma, Giant Cell / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016375:Antisense Elements (Genetics); D016228:Endothelial Growth Factors; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors