[Inhibition of growth and metastasis of human giant cell carcinoma of the lung by transfection of antisense VEGF121 cDNA].
OBJECTIVE
To explore the effects of blocking the VEGF/VEGF receptor paracrine pathway on growth and metastasis of human lung carcinoma cell line PG and to evaluate its potential application in gene therapy of cancer.


METHODS
The eukaryotic expression vectors bearing either sense-VEGF121 cDNA or antisense-VEGF121 cDNA was constructed and transfected into PG cells. In vitro and in vivo tests such as Northern blotting hybridization, Western blotting immunochemistry analysis, as well as xenografting in nude mice were used to analyze the effect of antisense-VEGF.


RESULTS
The transfectants stably expressing antisense VEGF121 were observed to produce markedly reduced 3.3 kb VEGF mRNA and 45 KD, 41 KD, 32KD VEGF proteins. When xenografted s.c. into nude mice, growth and metastasis of the antisense-VEGF transfected cell lines were greatly inhibited when compared with control cells.


CONCLUSIONS
Antisense VEGF gene significantly inhibited tumor growth and metastasis and may provide an experimental example for the development of antiangiogenic gene therapy.
Wu
X
X
Department of Pathology, Health Science Center, Peking University, Beijing 100083, China.
Zheng
J
J
Fu
J
J
You
J
J
Cui
X
X
Wang
J
J
Fang
W
W
Zhou
A
A
Wu
B
B
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D018286:Carcinoma, Giant Cell / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D016373:DNA, Antisense / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000235:genetics / Q000503:physiopathology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016373:DNA, Antisense; D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors