重组人内皮抑素对荷人肺腺癌裸鼠肿瘤微环境的调节作用

Effect of recombinant human endostatin on microenvironment of human lung adenocarcinoma

目的研究重组人内皮抑素对荷人肺腺癌裸鼠肿瘤微环境的调节作用。方法构建人肺腺癌裸鼠模型,重组人内皮抑素5mg/kg皮下给药14天。采用荧光素(TRlTC-Dex-tran)示踪法,荧光显微镜观察重组人内皮抑素处理后不同时间点荧光素在肿瘤中的分布,并计算肿瘤实质内部荧光素不能弥散到的面积相对于总面积的比例。结果给予处理14天后,对照组肿瘤内部血液弥散减少(低弥散面积占总面积的10.01%±4.50%),相对于第7和第21天显著增高(分别为1.49%±1.14%和2.90%±2.02%)。重组人内皮抑素能够在治疗的初始阶段抑制血液的弥散(低弥散面积占总面积的16.85%±4.03%),但第14天后这种抑制作用解除,肿瘤内部血液弥散反而增加(0.54%±0.32%,P=0.000),到第21天时则两组没有明显差别。讨论重组人血管内皮抑素能够暂时性的抑制肿瘤血管,此外重组人内皮抑素还能够调节肿瘤的内环境,在一段时间内增加了肿瘤内部血液弥散。

Purpose To study the effects of human recombinant human endostatin on the microenvironment of human lung adenocarcinoma. Methods BALB/c nude mice ously implanted with human adenocarcinoma cells and given rh-endostatin 5mg/kg s. c. when tumor grew to about 100mm^3, with days, and 21 days after the administration fravenous injection of TRITC-Dextran （155 normal saline was administered as control. of rh-endostatin, the mice were sacrificed 30 kD） 50mg/kg . Tumor samples were excised （rh-endostatin） were subcutanedaily for 14 days Seven days, 14 minutes after in- for the examination by fluorescence microscopy. The ratios of areas in the solid tumor where there was little TRITC - Dextran diffused were calculated. Results Fourteen days after administration of saline, the blood diffusion in the solid tumor was significantly lower than that on day 7 and day 21 （ 10. 01% ±4.50% versus 1.49% ± 1.14% and 2.90% ± 2.02% ）. Rhendostatin suppressed the blood diffusion at the tumor at the beginning of the treatment （ day 7, the ratio of areas where there was little fluorescein distributed was 16.8% ± 4. 02% ）. However, the blood diffusion increased by rh-endostatin 14 days after the treatment （P = 0. 000） and there was no difference of blood diffusion between the two groups on day 21. Conclusion Rh-endostatin can transiently inhibit the blood diffusion in human adenocarcinoma. Furthermore, it can modulate the microenvironment by increasing the blood diffusion in a short period.