纳米胶束对高表达CD44的肝癌干细胞作用的实验研究  

Effect of epirubicin and arsenic trioxide nanoparticles on liver cancer stem cells with CD44 high expression

作　　者：陈志奇[1] 梁暖 

机构地区：[1]大庆油田总医院胃肠外科,黑龙江大庆163112 [2]复旦大学附属中山医院青浦分院内镜室,上海201700

出　　处：《哈尔滨医科大学学报》2015年第6期494-497,共4页Journal of Harbin Medical University

摘　　要：目的探讨抗肿瘤药物纳米胶束对肝癌干细胞及移植瘤的作用。方法培养Hep G2人肝癌细胞株,利用CD44的抗体对所获细胞样品进行免疫分拣,逆转录PCR检测CD44 mRNA水平。肝癌干细胞接种于Balb/c裸小鼠脾脏,建立人肝癌移植瘤模型。制备表阿霉素及三氧化二砷纳米胶束。小鼠随机分为表阿霉素组、三氧化二砷组、表阿霉素纳米胶束组、三氧化二砷纳米胶束组及空白对照组(n=13)。用药后采用原位末端标记法检测肿瘤组织细胞凋亡;利用免疫组化观察移植瘤中血管内皮生长因子(VEGF)的表达,观察各组裸鼠移植瘤体积变化及抑瘤率。结果表阿霉素及三氧化二砷纳米胶束组细胞凋亡增加,与未用药对照组及表阿霉素及三氧化二砷组相比均差异显著(P<0.05);表阿霉素及三氧化二砷纳米胶束组传代移植瘤肿瘤新生血管生成减少,VEGF表达降低,与未用药对照组、表阿霉素及三氧化二砷组相比均差异有统计学意义(P<0.05)。表阿霉素及三氧化二砷纳米胶束组移植瘤瘤体体积减小,抑瘤率升高。结论表阿霉素及三氧化二砷纳米胶束能诱导细胞凋亡,降低VEGF的表达,缩小肿瘤体积、增加抑瘤率。Objective To study the effect of epirubicin and arsenic trioxide nanoparticles on liver cancer stern cells with CD44 high expression. Methods Human liver cancer cell line HepG2 were cultured. Immune cells were sorted by the use of CD44 antibody. Liver cancer stem cells with high expression of CD44 were obtained by reverse transcription PCR. The meta- static tumor model of liver cancer were established. Epirubiein and arsenic trioxide nanoparti- cles were prepared by sol-gel method. Rats were divided into 5 groups ： control group （ no treatment） , epirubicin nanoparticles group, arsenic trioxide nanoparticles group, epirubicin and arsenic trioxide group. After treated, TUNEL were performed to examine apoptosis. Expression of vascular endothelial growth factor （VEGF） were detected by immunohistochemical, and the volume change of tumor and tumor inhibition rates were observed. Results could produce a stronger apoptotis of tumor cells epirubicin and arsenic trioxide nanopaticles group was in- creased compared with epirubicin and arsenic trioxide group and control group （ P 〈 0.05 ）, ex- pression of VEGF was decreased. The volume of tumor and the tumor inhibition rates were sig- nificantly decreased in epirubicin and arsenic trioxide nanoparticles group compared with epiru- bicin and arsenic trioxide group and control group （ P 〈 0.05 ）. Conclusion Epirubicin and arsenic trioxide nanopaticles can induce the apoptosis of tumor, and inhibit the expression of VEGF and the growth of tumor.

关 键 词：肝癌干细胞 表阿霉素 纳米胶束 VEGF 三氧化二砷 凋亡 

分 类 号：R338[医药卫生—人体生理学]