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目的观察血管内皮生长因子(VEGF)-C反义寡核苷酸对胰腺癌裸鼠原位种植瘤模型淋巴管及血管生成的影响。方法建立人胰腺癌细胞株panc-1裸鼠原位种植瘤模型,将动物随机分为磷酸盐缓冲液(PBS)对照组(A组)、错义对照组(B组)和反义VEGF-C干预组(C组),每组10只,寡核苷酸用量为每次10 mg/kg体重,隔日1次,每周3次,共3周。建模4周后,处死动物,留取血清和瘤体标本,采用酶联免疫吸附试验(ELISA)、免疫组织化学染色法检测反义VEGF-C干预对VEGF-C分泌水平及种植瘤淋巴管和血管生成的影响。结果A、B和C组血清VEGF-C的蛋白表达水平分别为(237．5±41．5)、(221．5±52．3)、(108．6±14．9)ng/L,C组较A、B组明显为低(P＜0．01)；3组种植瘤内淋巴管密度分别为13．8±2．1、12．4±1．9和4．2±1．6,C组较A、B组显著减少(P＜0．01)；3组种植瘤内微血管密度分别为27．5±8．7、25．9±4．2和19．4±5．6,组间差异无统计学意义(P＞0．05)。结论反义寡核苷酸干预可以显著降低胰腺癌裸鼠原位种植瘤模型VEGF-C的表达水平,并对其淋巴管生成具有抑制作用。
Objective To observe the effect of vascular endothelial growth factor (VEGF) -C antisense oligonucleotide on lymphangiogenesis and angiogenesis in situ xenograft model of pancreatic cancer in nude mice. Methods The pancreatic cancer cell line panc-1 xenografts in nude mice were established. The animals were randomly divided into phosphate buffered saline (PBS) control group (group A), missense control group (group B) and antisense VEGF- C intervention group (group C) with 10 animals in each group. The dosage of oligonucleotide was 10 mg / kg body weight each time, every other day, 3 times a week for 3 weeks. Four weeks after modeling, animals were sacrificed and serum and tumor specimens were collected. ELISA and immunohistochemistry were used to detect the expression of VEGF-C and the growth of lymphatics And the effects of angiogenesis. Results The serum levels of VEGF-C in groups A, B and C were (237.5 ± 41.5), (221.5 ± 52.3) and (108.6 ± 14.9) ng / L, The density of lymphatic vessels in group C was significantly lower than that in group A and B (P <0.01). The density of lymphatic vessels in group C was 13.8 ± 2.1, 12.4 ± 1.9 and 4.2 ± 1, respectively. 6 in group C was significantly lower than that in group A and B (P <0.01). The microvessel density in the three groups was 27.5 ± 8.7,25.9 ± 4.2 and 19.4 ± 5, respectively. There was no significant difference between groups (P> 0.05). Conclusion Antisense oligodeoxynucleotides can significantly decrease the expression of VEGF-C in pancreatic cancer xenografts in nude mice and inhibit lymphangiogenesis.