Inhibitory effects of antisense oligodeoxynucleotide on expression of vascular endothelia growth factor by human hepatocarcinoma cells.
BACKGROUND
It is widely recognized that the growth of solid tumor depends on angiogenesis. Vascular endothelia growth factor (VEGF) is an endothelial cell-specific mitogen that promotes angiogenesis in solid tumor. Inhibition of angiogenesis is considered a promising approach for cancer therapy, and treatments including administration of antisense drugs and RNA interference for the VEGF gene are geared to the suppression of tumor angiogenesis.


METHODS
As a new approach for gene therapy of hepatocellular carcinoma (HCC), four groups of antisense oligodeoxynucleotide (ASODN) (A-Cap, A-AUG, A-UGA and A-Exon-3) were used to block the expression of VEGF, then VEGF mRNA and protein were detected by RT-PCR and Western blot.


RESULTS
After treatment with ASODN, the relative VEGF mRNA levels of A-Cap, A-AUG, A-UGA, and A-Exon-3 were decreased significantly to (32+/-9)%, (63+/-1)%, (86+/-3)%, and (70+/-5)%, respectively(F=64.18, P<0.001). The relative VEGF protein levels of A-Cap, A-AUG, A-UGA and A-Exon-3 were decreased significantly to (41+/-5)%, (59+/-3)%, (88+/-7)%, and (79+/-9)% respectively (F=60.64, P<0.001).


CONCLUSIONS
Among the four ASODNs, the ASODN for Cap structure showed the strongest inhibitory effect and that for A-UGA, the least (P<0.05 ). The inhibitory effect of ASODN on the expression of VEGF proteins was similar to that of VEGF mRNA expression.
Qiu
Meng-Biao
MB
Molecular Center, Second Affiliated Hospital of Jiangxi Medical College, Nanchang 330006, China.
Zhang
Ji-Xiang
JX
Liu
Liang-Ming
LM
Gong
Bang-Dong
BD
Wu
Bo-Lin
BL
Zhu
Shui-Shan
SS
Wen
Yi
Y
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A