[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.

CONCLUSION

Antisense VEGF gene significantly inhibited tumor growth and metastasis and may provide an experimental example for the development of antiangiogenic gene therapy.