重组人血管内皮抑素对Lewis肺癌抑制作用的实验研究

目的]研究重组人血管内皮抑素对Lewis肺癌的抑制作用。方法]采用MTT法检测不同剂量不同时间重组人血管内皮抑素对Lewis肺癌细胞增殖的影响;建立Lewis肺癌自发转移模型,将40只荷瘤小鼠随机分为重组人血管内皮抑素小、中、大剂量组(5、15、30 mg.kg-1.d-1)及对照组各10只,连续给药14 d,停药1周后处死小鼠,绘制肿瘤生长曲线,计算原发瘤抑瘤率;利用光镜和透射电镜技术,观察重组人血管内皮抑素对Lewis肺癌细胞以及对荷瘤小鼠血管内皮细胞和肿瘤细胞的形态学改变。结果]重组人血管内皮抑素对Lewis肺癌细胞增殖的抑制作用与浓度和作用时间呈正相关,400 ng处理72 h后的抑制率为(68.4±1.5)%,与处理24 h后的抑制率(21.9±2.1)%比较,差异有显著性意义(P<0.05)。各给药组肿瘤生长均较对照组缓慢,小、中、大剂量组的抑瘤率分别为28.2%、49.7%、52.8%。各给药组小鼠瘤组织内均有大面积坏死,血管内皮细胞和肿瘤细胞均发生早期凋亡的改变,且具有剂量依赖性。结论]重组人血管内皮抑素对Lewis肺癌的抑制作用可能表现为对肿瘤细胞和毛细血管内皮细胞的双重抑制作用。

Inhibitory effect of recombinant human endostatin on Lewis lung carcinoma

Objective] To observe the inhibitory effect of recombinant human endostatin(rhES) on Lewis lung carcinoma.Methods] The inhibition of Lewis lung carcinoma cell proliferation was measured by MTT assay after treatment with rhES in lung cancer cells.Lewis lung carcinoma cell were inoculated subcutaneously into C57BL/6 mice.Forty mice were randomly divided into experimental groups(rhES of 5,15,30 mg·kg-1·d-1) and control group.On the 21th day,the m ice were killed.Tumor growth curve was described and the inhibitory rate of primary tumor was measured.Ultrastructure of Lewis lung carcinoma cells and vascular endothelial cells were observed by transmission electron microscope.Results] rhES significantly inhibited Lewis lung carcinoma cell proliferation with time-dependence.Inhibitory rate of tumor cell proliferation with rhES 400 ng after 72 h and 24 h was(68.4±1.5)% and(21.9±2.1)%(P<0.05).Tumor growth curves in experimental groups were smooth compared with control group.Inhibitory rates of primary tumor of mice with rhES 5,15,30 mg·kg-1·d-1 was 28.2%,49.7%,52.8% respectively.Tumor cells were necrosis in a large area in experimental groups,and apoptosis occurred in carcinoma cells and vascular endothelial cells.According with the more drug doses,there was the more effect.Conclusion] rhES can inhibit Lewis carcinoma cell proliferation and angiogenesis of mice Lewis lung carcinoma.