Anti-angiogenesis effect of generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide on breast cancer in vitro.
OBJECTIVE
To study the effects of the generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide (G4PAMAM/VEGFASODN) compound on the expressions of vascular endothelial growth factor (VEGF) and its mRNA of breast cancer cells and on the inhibition of vascular endothelial cells.


METHODS
We examined the morphology of G4PAMAM/VEGFASODN compound and its pH stability, in vitro transfection efficiency and toxicity, and the expressions of VEGF and its mRNA. Methyl thiazolyl tetrazolium assay was used to detect the inhibitory function of the compound on vascular endothelial cells.


RESULTS
The compound was about 10 nm in diameter and was homogeneously netlike. From pH 5 to 10, it showed quite a buffered ability. The 48-h transfection rate in the charge ratio of 1:40 was 98.76%, significantly higher than that of the liposome group (P<0.05). None of the transfection products showed obvious toxicity on the cells. The expressions of both VEGF protein and its mRNA after G4PAMAM/VEGFASODN transfection decreased markedly.


CONCLUSIONS
With a low toxicity, high safety, and high transfection rate, G4PAMAM/VEGFASODN could be a promising gene vector. Specifically, it inhibits VEGF gene expression efficiently, laying a basis for further in vivo animal studies.
Gu
Shan-zhi
SZ
MOE Key Laboratory of Environment and Genes Related to Diseases, the First Affiliated Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
Zhao
Xin-han
XH
Zhang
Ling-xiao
LX
Li
Li
L
Wang
Zhi-yu
ZY
Meng
Min
M
An
Gai-li
GL
D020533:Angiogenesis Inhibitors / Q000235:genetics*; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050091:Dendrimers; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D046529:Microscopy, Electron, Transmission; D009757:Nylons; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure
D020533:Angiogenesis Inhibitors; D050091:Dendrimers; D009757:Nylons; D020319:Oligodeoxyribonucleotides, Antisense; C520550:PAMAM-G4; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A