BACKGROUND: It is widely recognized that the growth of solid tumor depends on angiogenesis. Vascular endothelia growth factor (VEGF) is an endothelial cell-specific mito- gen 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 hepato- cellular carcinoma (HCC), four groups of antisense oli- godeoxynucleotide (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)% respec- tively (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.
Meng-Biao Qiu, Ji-Xiang Zhang, Liang-Ming Liu, Bang-Dong Gong, Bo-Lin Wu, Shui-Shan Zhu and Yi Wen Nanchang, China Molecular Center, Second Affiliated Hospital of Jiangxi Medical College, Nanchang 330006, China