Abstract: Objectives To study the effects of pU- vascular endothelial growth factor (VEGF) short interfering RNA (siRNA) on the formation and apoptosis of malignant melanoma in models of nude mice and its mechanism. Methods The siRNA eukaryotic expression vector for VEGF was constructed, then transfected into A375 (a human malignant melanoma cell line) by electroporation. The nude mice models of malignant melanoma were constructed. The protein expression of VEGF and factor Ⅷ related antigen (FⅧRAg) specific for vascular endothelial cells was detected by immunohistochemical technique and morphological quantitative analysis. Microvessel density (MVD) was counted based on the endothelial cells positively stained with anti-FⅧRAg antibody. The apoptosis of the neoplasms in nude mice was quantitatively determined by TdT mediated dUTP nick end labeling (TUNEL). Results Both the number and the growth speed of the neoplasm formation were lower in the experimental group than those in the controls (both P<0.01). VEGF expression and MVD significantly decreased in experimental group than those in the controls (P<0.01). Numerous apoptotic cells were found in the experimental groups,but few in the controls. The apoptotic indices were significantly higher in the experimental group than those in the controls (P<0.01). Conclusions The delivery of siRNA directed against VEGF is shown to inhibit the growth of malignant melanoma in vivo, suggesting that siRNA-based, VEGF targeting strategy might benefit the research of gene therapy for malignant melanoma.

Key words: Melanoma,experimental, pU-VEGF-siRNA, Apoptosis