摘要
目的观察酵母表达重组人内皮抑素(recombinant human endostatin, rhES)对小鼠肺腺癌LA795原位肿瘤微血管生成及肺转移的抑制作用。方法对含有人内皮抑素基因的重组酵母菌株进行诱导表达及纯化rhES;将接种LA795小鼠肺腺癌细胞的T739小鼠随机分成两组,每组各10只,于接种后第6日起给予rhES和磷酸缓冲盐液(PBS)皮下注射,每日1次,连续14 d;观察两组小鼠原位肿瘤微血管生成情况及肺部肿瘤转移情况。结果经甲醇诱导酵母转化子表达rhES,并用肝素亲和层析的方法获得纯化的rhES;治疗结束后用免疫组化方法观察两组小鼠原位肿瘤微血管密度发现rhES治疗组肿瘤微血管密度明显小于PBS对照组(P<0.01);观察两组小鼠肺部发现rhES治疗组小鼠肺部未见有明显肿瘤转移病灶,而PBS对照组小鼠肺部可见大量散在肿瘤转移病灶;两组小鼠肺湿重比较具有显著性差异(P<0.01)。结论rhES具有良好的生物学活性,显著抑制了小鼠肺腺癌LA795肿瘤血管生成,并能有效抑制肿瘤的肺部转移。
Objective To study the inhibitory effect of recombinant human endostatin (rhES) on the angiogenesis and lung metastasis of mouse lung adenocarcinoma LA795. Methods The recombinant yeast strain containing the gene sequence encoding highly soluble rhES was induced by methanol for rhES production, which was purified with heparin affinity chromatography. T739 mice with subcutaneous inoculation of LA795 cells were randomized into 2 groups (10 in each group) to receive injection of either rhES (20 mg/kg·b.w. per day) or PBS in the same volume for 14 consecutive days starting from the sixth day after the inoculation. The angiogenesis and lung metastasis of the implanted tumors were subsequently observed. Results Purified rhES was successfully obtained. As shown by immunohistochemistry, the tumors in the mice receiving rhES treatment exhibited less density of the microvessels than those in the PBS-treated mice did (P<0.01). Pathological examination of the lung tissue of the mice in rhES group found no visible signs of tumor metastasis, which, in contrast, was widespread in PBS group. The weight of the lungs was also significantly different (P<0.01). Conclusion rhES possesses good biological properties and can potently inhibit the angiogenesis and lung metastasis of mouse lung adenocarcinoma LA795.
出处
《第一军医大学学报》
CSCD
北大核心
2003年第1期30-33,共4页
Journal of First Military Medical University
基金
广东省科委重点科技攻关项目(99G172001)~
