目的:观察TNP-470和重组人内皮抑素（recombinant human endostatin,rhES）联合治疗对小鼠肺腺癌LA795肿瘤生长的抑制作用。方法: 用甲醇诱导能高效分泌表达重组人内皮抑素（rhES）的毕赤酵母菌株分泌表达rhES，将皮下接种LA795肺腺癌细胞的T739雄性近交系小鼠随机分成3组，每组各10只，分别给予PBS，rhES及TNP-470+rhES皮下注射，每日1次，连续14 d；观察各组小鼠肿瘤生长情况，游标卡尺测量肿瘤体积大小。断颈处死小鼠，原位肿瘤免疫组化观察肿瘤内部微血管密度（microvessel density, MVD）。结果: 经甲醇诱导，毕赤酵母重组菌分泌表达rhES，并应用肝素亲和层析将其纯化；动物试验显示与PBS对照组比较，rhES治疗组及rhES＋TNP 470治疗组均明显抑制小鼠肿瘤的生长（P<0.01），TNP-470+rhES组与rhES组比较亦有显著性差异（P<0.01）。原位肿瘤免疫组化显示联合治疗组抑制血管生成更显著（P<0.01）。结论: TNP-470联合rhES治疗对小鼠肺腺癌LA795生长的抑制效果比单独使用rhES的治疗效果更佳，具有良好的协同治疗作用

Objective:To investigate the combined inhibitive effect of TNP-470 and rhES on the growth of lung adenocarcinoma LA795 in T739 mice. Methods: The purified rhES was acquired by using methanol to induce the recombinant pichia pastoris. GS115 and heparin affinity chromatography. The T739 mice inoculated with LA795 cells were randomized into three groups, 10 mice per group, one group was injected with PBS for 14 days, the other two groups were respectively treated with rhES and TNP-470+rhES. To observe the tumor growth in different groups, and the tumor volume was measured with caliper. The microvessel density(MVD) of tumors were measured by using immunohistochemistry. Results: The purified rhES was acquired. In compared with PBS group, the tumor growth of other two groups was inhibited significantly. And the tumor volume of TNP-470+rhES group are smaller than the rhES group (P<0.01). immunohistochemistry showed the combined therapy has more inhibitory effect on angiogenesis. Conclusion: The combined treatment with TNP-470 and rhES showed more than additive effect in tumor growth inhibition when compared with treatment with individual antiangiostatic protein rhES.

广东省科委九五重点科技攻关项目资助（99G172001）