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目的探讨Oligofectamine介导的血管内皮生长因子(vascular endothelial cell growthfactor,VEGF)反义寡核苷酸(antisense oligodeoxynucleotides,ASODN)转染对人胆囊癌细胞GBC-SD裸鼠移植瘤的VEGF表达和血管形成的影响。方法裸鼠接种GBC-SD细胞建立移植瘤模型,随机分为A、B、C三组,各组裸鼠在接种1周后,分别给于200μl磷酸缓冲液(PBS)、VEGFSODN100μg+Oligofectamine0.5μl及VEGF ASODN100μg+Oligofectamine0.5μl,每3天1次,连续治疗5周,观察各组裸鼠的成瘤性、体积及瘤重的变化,各组移植瘤中VEGF表达及微血管密度(MVD)变化。结果三组裸鼠3周时的成瘤率,C组显著低于A、B两组(P<0.05),6周时各组的成瘤率无差异。各组移植瘤6周时的体积和瘤重相比C组显著低于A、B两组(P<0.05),C组的抑瘤率为(50.79±9.19)%。A、B两组移植瘤VEGF表达及MVD均无显著性差异(P>0.05),而C组移植瘤VEGF的表达较A、B两组明显减弱(P<0.05),MVD明显小于A、B两组(P<0.05)。结论VEGF ASODN在体内能显著抑制人胆囊癌裸鼠移植瘤的增殖,降低其在裸鼠体内的成瘤性,抑制VEGF在蛋白水平的表达,减少裸鼠移植瘤中血管的形成,降低微血管密度。
Objective To investigate the effect of Oligofectamine-mediated vascular endothelial cell growth factor (VEGF) antisense oligodeoxynucleotides (ASODN) transfection on VEGF expression and angiogenesis in human gallbladder carcinoma cell line GBC-SD in nude mice. Impact. Methods The nude mice were inoculated with GBC-SD cells to establish a xenograft model and randomly divided into A, B, and C groups. After 1 week of inoculation, nude mice in each group were given 200 μl phosphate buffer (PBS), VEGFSODN 100 μg, and Oligofectamine 0.5 μl, respectively. And VEGF ASODN100μg+Oligofectamine0.5μl, once every 3 days, continuous treatment for 5 weeks, observed the tumorigenicity, volume and tumor weight of nude mice in each group, the expression of VEGF and microvessel density (MVD) in all groups. . Results The tumor formation rate of three groups of nude mice at 3 weeks was significantly lower in group C than in group A and B (P<0.05), and there was no difference in the rate of tumor formation in each group at 6 weeks. The volume and tumor weight of transplanted tumors in each group at 6 weeks were significantly lower than those in group A and B (P<0.05), and the inhibition rates in group C were (50.79±9.19)%. There was no significant difference in VEGF expression and MVD between the two groups (P>0.05). The expression of VEGF in group C was significantly lower than that in group A and B (P<0.05). The MVD was significantly smaller than that of A and B. Two groups (P<0.05). Conclusion VEGF ASODN can significantly inhibit the proliferation of human gallbladder carcinoma xenografts in nude mice, reduce tumorigenicity in nude mice, inhibit the expression of VEGF at the protein level, reduce the formation of blood vessels in nude mice, and reduce the microvessel density. .