摘要
目的:观察半乳糖基壳聚糖(GC)/5-氟尿嘧啶(5-FU)纳米粒抑制小鼠原位肝癌移植模型的疗效及机制。方法:合成GC/5-FU纳米粒,建立小鼠原位肝癌移植模型,通过动物实验观察GC/5-FU纳米粒治疗小鼠原位肝癌移植模型的疗效,通过原位末端标记法(TUNEL法)检测肝癌的凋亡。结果:GC/5-FU纳米粒成功合成,呈规则的球形,表面光滑,大小均匀,纳米粒间无粘连。实验结束时,小鼠的肝癌组织称重,进行方差分析发现GC/5-Fu的瘤重为(0.4361±0.1153)g,5-Fu组为(0.7932±0.1283)g,GC为(1.3989±0.2125)g,和对照组为(1.5801±0.2821)g,4组瘤重之间差异有显著的统计学意义(P<0.01)。GC/5-FU组和5-FU组的瘤重明显小于GC组及对照组,差异有统学意义(P<0.01);GC/5-FU的瘤重又显著小于5-Fu组(P<0.01)。观察各组小鼠的生存期发现对照组的中位生存时间为12d,GC组为13d,5-FU为17d,而GC/5-FU组最高为30d。GC/5-FU组的生存时间最长。通过TUNEL法观察肝癌细胞的凋亡发现GC/5-FU组的平均凋亡指数(AI)为21.34%较5-FU组的14.74%明显增高(P<0.05),均较GC组和对照组明显增高,而GC组和对照组间的AI无明显差异(P>0.05)。结论:GC/5-FU纳米粒在体内对小鼠原位肝癌具有明显抑制作用,较5-FU明显增强。其机理可能与GC能通过细胞膜将5-FU从细胞外转移到细胞内,增强5-FU对肝癌细胞的凋亡。
Objective： To observe the efficacy and mechanism of hepatocellular carcinoma in the orthotopic transplant mouse model with galactosylated chitosan（GC） / 5-fluorouracil（5-FU） nanoparticles.Methods： The GC/5-FU nanoparticles were prepared,the hepatocellular carcinoma in the orthotopic transplant mouse model were established,the apoptosis in liver cancer by TdT-mediated dUTP nick end labeling（TUNEL） were detected.Results： GC/5-FU nanoparticles were successfully synthesized in spherical,smooth surface,uniform size,no adhesion between the nanoparticles.At the end of the experiment,the weight of the tumor in each group was： 0.4361± 0.1153 g in GC/5-FU group,0.7932±0.1283 g in 5-FU group,1.3989±0.2125 g in GC group and 1.5801±0.2821 g in control group.The differences between the groups was statistically significant（P0.01）.The tumor weight in the GC/5-FU group and the 5-FU were significantly less than those in the GC group and control group（P0.01）;tumors in the GC/5-FU group were significantly less compared with the 5-FU group（P0.01）.The median survival for control,GC,5-FU and GC/5-FU groups were 12 d,13 d,17 d,and 30 d,respectively.The longest median survival time was seen in the GC/5-FU group（P0.01）.Quantification of the apoptosis index（AI） identified a statistically significant difference between the GC/5-FU group（AI = 21.34%） and the 5-FU group（AI = 14.74%,P0.05）,both of which were higher than that in the GC and control groups（P0.01）.Conclusion： GC/5-FU nanoparticles can also significantly inhibit the tumor growth in the orthotropic liver cancer mouse model,and this in vivo effect is stronger than that of 5-FU alone.GC facilitates intracellular transport of 5-FU,and increases the apoptosis of liver cancer induced by 5-FU.
出处
《现代生物医学进展》
CAS
2012年第35期6819-6823,共5页
Progress in Modern Biomedicine
基金
上海市自然科学基金项目(09ZR1424700
114119a4700)
闵行区卫生局科学基金项目(2009MW28)
关键词
半乳糖基壳聚糖
纳米粒
5-氟尿嘧啶
肝癌
凋亡
Galactosylated chitosan
Nanoparticles
5-fluorouracil
Liver cancer
Apoptosis
