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目的观察脂质体介导的血管内皮生长因子C(VEGF-C)反义寡核苷酸对肺癌裸鼠皮下种植瘤模型微淋巴管生成的影响。方法接种人肺腺癌细胞株A549建立30只BALB/C小鼠皮下肺癌模型,24 h内分别皮下注射磷酸盐缓冲液(PBS组)、正义寡核苷酸(SODN组)或反义寡核苷酸(AODN组)进行治疗,每组10只。观察小鼠肿瘤的生长情况。建模4周后,处死动物,留取瘤体标本,采用RT-PCR、Western blot和免疫组织化学方法检测VEGF-C反义寡核苷酸对种植瘤中VEGF-C表达水平和微淋巴管生成的影响。结果AODN组种植瘤内VEGF-C mRNA和蛋白表达量明显少于PBS组和SODN组(P<0.05)。AODN组种植瘤内微淋巴管密度也明显少于PBS组和SODN组(P<0.01)。结论脂质体介导的VEGF-C反义寡核苷酸可以显著降低肺癌裸鼠皮下种植瘤VEGF-C表达水平,并对其微淋巴管生成具有较强抑制作用。
Objective To observe the effect of liposome-mediated vascular endothelial growth factor C (VEGF-C) antisense oligonucleotide on lymphangiogenesis in lung cancer xenografts in nude mice. Methods Thirty BALB / C mouse models of subcutaneous lung cancer were established by inoculating human lung adenocarcinoma cell line A549 and were injected subcutaneously with phosphate buffered saline (PBS), sense oligonucleotide (SODN) or antisense oligonucleotide (AODN group) for treatment, 10 in each group. Observation of tumor growth in mice. Four weeks after modeling, animals were sacrificed and tumor specimens were collected for the detection of VEGF-C expression in VEGF-C antisense oligonucleotides and lymphatic vessels by RT-PCR, Western blot and immunohistochemistry Generated effects. Results The expression of VEGF-C mRNA and protein in AODN group was significantly less than that in PBS group and SODN group (P <0.05). The density of lymphatic vessels in AODN group was also significantly less than that in PBS group and SODN group (P <0.01). Conclusion Liposome-mediated VEGF-C antisense oligonucleotide can significantly reduce the expression of VEGF-C in subcutaneously implanted lung cancer in nude mice and has a strong inhibitory effect on lymphangiogenesis.