重组血管内皮抑素对荷人食管鳞癌裸鼠VEGF-C和LYVE-1表达水平的影响

Influence by recombinant endostatin on expression levels of VEGF-C and LYVE-1 in nude mice bearing human esophageal squamous carcinoma

目的研究重组血管内皮抑素(ES)对荷人食管鳞癌裸鼠血管内皮生长因子-C(VEGF-C)和淋巴管内皮细胞透明质酸受体-1(LYVE-1)的调节作用。方法构建人食管鳞癌裸鼠模型,6只瘤周皮下注射ES稀释液荷瘤裸鼠作为A组,6只瘤周皮下注射生理盐水荷瘤裸鼠作为B组,6只正常裸鼠作为C组,比较三组血清LYVE-1、VEGF-C的表达水平,观察ES对荷瘤裸鼠LYVE-1和VEGF-C基因表达的影响。结果 A、B组血清VEGF-C水平分别为(155.26±10.24)、(180.23±15.64)pg/L,均高于C组的(103.15±13.20)pg/L,差异具有统计学意义(P<0.01);A组血清VEGF-C水平低于B组,差异具有统计学意义(P<0.05)。A、B组血清LYVE-1水平分别为(65.32±16.29)、(90.58±10.67)pg/L,均高于C组的(28.31±10.36)pg/L,差异具有统计学意义(P<0.01);A组血清LYVE-1水平低于B组,差异具有统计学意义(P<0.05)。A、B组组织内VEGF-C、LYVE-1的PCR扩增倍数均高于C组,差异具有统计学意义(P<0.01);A组组织内VEGF-C、LYVE-1的PCR扩增倍数低于B组,差异具有统计学意义(P<0.05)。结论通过重组ES对TE-1食管鳞癌细胞荷瘤裸鼠干预,重组ES不仅抑制肿瘤新生血管的生成,而且重组ES可能通过抑制肿瘤组织内VEGF-C和LYVE-1的表达,对肿瘤新生淋巴管的发生起到抑制作用。

Objective To research regulating effect by recombinant endostatin（ES）on vascular endothelial growth factor-C（VEGF-C）and lymphatic vessel endothelial hyaluronan receptor-1（LYVE-1）in nude mice bearing human esophageal squamous carcinoma. Methods In establishment of nude mice model bearing human esophageal squamous carcinoma, there were 6 nude mice bearing tumor as group A receiving subcutaneous injection of ES diluents in peripheral tumor skin, 6 nude mice bearing tumor as group B receiving subcutaneous injection of normal saline in peripheral tumor skin, and 6 normal nude mice as group C. Comparison was made on serum expression levels of LYVE-1 and VEGF-C in the three groups. Observation was made on influence byES on gene expression of LYVE-1 and VEGF-C in nude mice bearing tumor. Results Group A and group B had serum VEGF-C level respectively as（155.26±10.24） and（180.23±15.64） pg/L, which were all higher than（103.15±13.20） pg/L in group C, and their difference had statistical significance（P〈0.01）. Group A had lower serum VEGF-C level than group B, and their difference had statistical significance（P〈0.05）. Group A and group B had serum LYVE-1 level respectively as（65.32±16.29） and（90.58±10.67） pg/L, which were all higher than（28.31±10.36） pg/L in group C, and their difference had statistical significance（P〈0.01）. Group A had lower serum LYVE-1 level than group B, and their difference had statistical significance（P〈0.05）. Group A and group B both had higher PCR expanding fold of tissue LYVE-1 and VEGF-C than group C, and the difference had statistical significance（P〈0.01）. Group A had lower PCR expanding fold of tissue LYVE-1 and VEGF-C than group B, and the difference had statistical significance（P〈0.05）. Conclusion Intervention by recombinant ES for nude mice bearing TE-1 esophageal squamous carcinoma showed that recombinant ES can not only inhibit neovascularization in tumor, but also show inhibiting effect for lymphangiogenesis in tumor through inhibition of VEGF-C and LYVE-1 in tumor tissue.