摘要
目的:探讨血管生成抑制剂SU6668联合5-Fu对人结肠癌肝转移的抑制作用。方法:将结肠癌HT-29细胞注入裸鼠脾脏,建立结肠癌肝转移模型。将裸鼠随机分为联合治疗组、SU6668组、5-Fu组和对照组4组。治疗6周后,处死裸鼠,计数肝转移率和肝转移结节数。采用免疫组化SABC法和图像分析系统对肝转移肿瘤组织的微血管密度(microvessel density,MVD)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、碱性成纤维细胞生长因子(base fibroblast growth factor,bFGF)的表达进行定量分析。结果:各组转移率依次下降,差异有统计学意义(P<0.01);在肝转移结节数目比较上,对照组结节数大于20个时各组裸鼠所占比例差异有统计学意义(P<0.01)。联合治疗组和SU6668组分别与5-Fu组及对照组相比,MVD均显著减少(P<0.05)。联合治疗组、SU6668组、5-Fu组与对照组比较,VEGF、bFGF均显著降低,且联合治疗组、SU6668组、5-Fu组3组间差异有统计学意义(P<0.05)。结论:SU6668通过抗血管生成抑制结肠癌的肝转移,与5-Fu联合应用具有协同效应,为安全有效的抗肿瘤策略。
Objective： To study the effect of the angiogenesis inhibitor SU6668 combined with 5-Fu on liver metastasis in human colon cancer. Methods： The human colon cancer cell line, HT-29 cells were injected intrasplenicaUy into BALB/c nude mice to make the diffuse liver metastasis model. Mice were randomly divided into four groups： SU6668 treatment group, 5-Fu treatment group, SU6668 ＋ 5-Fu treatment group and control group. Animals were sacrificed after 7 weeks, and their livers were processed for histological examination. Liver metastasis rate and tumor foci in liver were counted. Tumor microvessel density（MVD） and vascular endothelial growth factor（VEGF）, and base fibroblast growth factor （bFGF） were determined by the inmnmohistochemistry SABC method with an image analysis system. Results： SU6668 combined with 5-Fu and SU6668 alone displayed a significant inhibitory effect on liver metastasis compared with the control （P 〈0.01）, and a significant decrease of the expression of VEGF and bFGF compared with the control（ P 〈0.05）. The expression of MVD was also inhibited by SU6668 in combination with 5-Fti or SU6668 alone compared with the control（ P 〈 0.05）. Conclusion： The angiogenesis inhibitor SU6668 in combination with 5-Fu has an additive effect and inhibitory activity against liver metastasis of human colon cancer, therefore, it might be a safe and effective antitumor strategy.
出处
《山东大学学报（医学版）》
CAS
北大核心
2007年第2期168-170,174,共4页
Journal of Shandong University:Health Sciences
