恩度联合放疗对鼻咽癌裸鼠成瘤的抑制作用及机制

The Study of Irradiation in Combination with Endostar Therapy for Human Nasopharyngeal Carcinoma Xenografts in Nuke Mice

目的:观察恩度联合放疗对鼻咽癌裸鼠成瘤的抑制作用及对血管内皮生长因子(VEGF)和生存素SurvivinmRNA表达的影响。方法:建立鼻咽癌裸鼠成瘤模型,成瘤后随机分为对照组、恩度组、放疗组和恩度+放疗联合组(联合组),观察各组移植瘤的生长速度和瘤体大小的变化。4周后处死裸鼠摘取瘤体,电镜观察各组肿瘤凋亡情况,应用实时荧光定量PCR检测各组瘤体组织中的VEGF和Survivin mRNA的表达水平。结果:联合组肿瘤体积增长受到明显抑制,对照组生长迅速,恩度组与放疗组居中。恩度组、放疗组和联合组的VEGF表达水平均低于对照组,联合组低于放疗组,差异均有统计学意义(P<0.05或P<0.01),放疗组和联合组的Survivin表达水平均低于对照组,联合组低于放疗组,差异均有统计学意义(P<0.05或P<0.01)。成瘤组织中VEGF与Survivin的表达呈正相关(r=0.679,P<0.01)。结论:恩度联合放疗能明显抑制鼻咽癌裸鼠移植瘤的生长,这种作用可能与VEGF和Survivin表达下调有关。

Objective： To observe the inhibitory effect of endostar combined with radiotherapy on transplanted CNEI nasopharyngeal carcinoma （NPC） in BALB/c nude mice, and explore the relationship of this inhibitory effect with the expression level of vascular endothelial growth factor （VEGF） and apoptosis protein-Survivin. Methods： The transplanted tumor model of human CNE1 nasopharyngeal carcinoma was established in nude mice. Model mice were randomly divided into control group, endostar treatment group, radiation group and endostar＋radiation group. The growth characteristics of transplanted tumor were recorded in four groups. After 4 weeks mice were sacrificed and removed the tumor. The morphological changes of cell apoptosis were observed by transmission electron microscopy. The expression levels of VEGF and Survivin mRNA of tumor tissues were detected by Real-time quantitative PCR. Results： There was a significant tumor growth inhibitory effect in endostar＋radiation group, followed by endostar treatment group and radiation group. The rapid tumor growth was found in control group. The expression levels of VEGF were significantly lower in endostar treatment group, radiation group and endostar＋ radiation group. The expression level of VEGF was significantly lower in endostar＋radiation group than that of radiation group （P 〈 0.05 or P 〈 0.01）. The expression levels of Survivin were significantly lower in radiation group and endostar＋radiation group than that of control group, and the level was significantly lower in endostar＋radiation group than that of radiation group （P 〈 0.05 or P 〈 0.01）. The expression of VEGF was positively correlated with that of Survivin in tumor tissue （r = 0.679, P 〈 0.01）. Conclusion： Endostar in combination with radiotherapy could significantly inhibit the NPC transplantation tumor in nude mice, which may be related with the down-regulation of expression levels of VEGF and Survivin.