叶酸修饰多西紫杉醇纳米脂质体对肝癌Bel-7402细胞的体内外靶向性研究
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篇名: 叶酸修饰多西紫杉醇纳米脂质体对肝癌Bel-7402细胞的体内外靶向性研究
TITLE:
摘要: 目的:研究叶酸(FA)修饰多西紫杉醇(DOC)纳米脂质体(L-DOC-FA)对肝癌Bel-7402细胞的体内外靶向性。方法:采用细胞活性检测试剂盒分别检测0、1、2、5、10、20 μg/ml DOC、L-DOC、L-DOC-FA培养细胞24 h后的细胞活性,计算细胞存活率;利用荧光素异硫氰酸酯标记L-DOC、L-DOC-FA,检测肝癌细胞Bel-7402对L-DOC、L-DOC-FA的摄取率;125I标记L-DOC、L-DOC-FA,检测其在皮下肿瘤组织中的含量;取28只Balb/c裸鼠,背部ih肝癌细胞悬液复制肿瘤模型,模型复制成功后将裸鼠分为空白对照(生理盐水)组、DOC(3 mg/kg)、L-DOC(3 mg/kg,以DOC计)和L-DOC-FA(3 mg/kg,以DOC计)组,每天尾iv相应药物1次,连续30 d,测定各组裸鼠肿瘤的相对瘤体积。结果:DOC、L-DOC、L-DOC-FA对肝癌Bel-7402细胞活性均有抑制作用,细胞存活率降低且呈浓度依赖性;与DOC、L-DOC比较,L-DOC-FA作用后细胞活性更低,细胞存活率降低(P<0.01)。细胞对L-DOC、L-DOC-FA的摄取率大小为L-DOC-FA(69.5%)>L-DOC(31.2%),差异有统计学意义(P<0.01);肿瘤组织中L-DOC-FA含量比L-DOC含量高(P<0.01); 3 mg/kg L-DOC-FA比相同质量浓度L-DOC、DOC抑瘤效果更明显,相对瘤体积更小(P<0.01)。结论:L-DOC-FA在体内外均对肝癌Bel-7402细胞有明显的主动靶向性,并表现出了很好的体内外肿瘤靶向抑制效果。
ABSTRACT: OBJECTIVE: To study the targeting of folic acid (FA)-modified docetaxel (DOC) nano-liposome (L-DOC-FA) to hepatocellular carcinoma Bel-7402 cells in vivo and in vitro. METHODS: The cell viability and survival rate of Bel-7402 cells was tested by CCK-8 kit after treated with 0, 1, 2, 5, 10 and 20 μg/ml DOC, L-DOC and L-DOC-FA for 24 h. And then, the fluorescein isothiocyanate was used to label L-DOC and L-DOC-FA nano-liposome, and the rate of L-DOC and L-DOC-FA absorbed by hepatocellular carcinoma Bel-7402 cells were detected. 125I was used to label L-DOC and L-DOC-FA nano-liposome, and then the contents of them in the subcutaneous tumor tissues were detected. 28 Balb/c naked mice were selected and given liver cell suspension via back ih to induce tumor model. After modeling, naked mice were divided into blank control group (normal saline), DOC group (3 mg/kg), L-DOC (3 mg/kg, by DOC) and L-DOC-FA (3 mg/kg, by DOC). They were given relevant medicine intravenously once a day for consecutive 30 d. The relative tumor volume in naked mice was detected. RESULTS: DOC, L-DOC and L-DOC-FA all inhibited the cell viability of Bel-7402 cells, the survival rate of cells decreased in concentration-dependant manner; compared with DOC and L-DOC, the cell viability decreased after treated with L-DOC-FA, the survival rate of cells decreased (P<0.01). The rate of L-DOC and L-DOC-FA absorbed by Bel-7402 cells in descending order as L-DOC-FA (69.5%)>L-DOC (31.2%), with statistical significance (P<0.01). The content of L-DOC-FA in tumor was significantly more than that of L-DOC (P<0.01). In addition, 3 mg/kg L-DOC-FA showed better inhibitory effect than 3 mg/kg L-DOC and DOC on tumor, and the relative tumor volume was smaller (P<0.01). CONCLUSIONS: L-DOC-FA has obvious targeting to Bel-7402 cells in vivo and in vitro, and shows good inhibitory effect on tumor in vivo and in vitro.
期刊: 2016年第27卷第10期
作者: 计竹娃,钦富华,夏晓静,胡英
AUTHORS: JI Zhuwa,QIN Fuhua,XIA Xiaojing,HU Ying
关键字: 叶酸修饰纳米脂质体;多西紫杉醇;靶向性;肝癌Bel-7402细胞;肿瘤抑制;裸鼠
KEYWORDS: Folic acid-modified nano-liposome; Docetaxel; Targeting; Liver cancer Bel-7402 cells; Tumor inhibition; Naked mice
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