脂蟾毒配基PLGA-TPGS纳米粒对小鼠肝癌异位移植瘤抑制作用的研究

发布时间：2019-06-07 17:26

【摘要】：目的:考察脂蟾毒配基乙交酯丙交酯共聚物-维生素E聚乙二醇1000琥珀酸酯(PLGA-TPGS)纳米粒(RPTN)在体内对荷腹水型肝癌高淋巴道转移细胞HCa-F小鼠异位移植实体瘤的抑制作用。方法:为保证体内给药的安全性和确定给药剂量,考察RPTN和脂蟾毒配基溶液(RS)在小鼠体内静脉给药途径的半数致死量(LD50)。建立荷HCa-F细胞小鼠肝癌异位移植实体瘤模型后分为6组,分别为空白对照组、空白纳米粒组、5-氟尿嘧啶溶液(FS)组、RS组、脂蟾毒配基乙交酯丙交酯共聚物(PLGA)纳米粒(RPN)组、RPTN组,尾静脉给药,每天1次,连续给药7 d;在停药次日,处死小鼠后剥离实体瘤,称重并测量实体瘤体积,根据公式计算实体瘤体积增长量和抑瘤率;将实体瘤固定后进行常规石蜡切片包埋,苏木素曙红(HE)染色观察,全面评价RPTN在小鼠体内的抑瘤效果。结果:RPTN和RS小鼠静脉给药LD50分别为38.2 mg·kg-1和18.9 mg·kg-1,表明RPTN在一定程度上可减轻RBG在小鼠体内的毒性作用,相比RS更安全。小鼠体内抗肿瘤试验中给药7 d后,FS组、RPN组、RPTN组的实体瘤体积增长量与空白对照组相比明显减小(P0.05或P0.01),RPTN组抑瘤率为64.93%,明显高于RPN组(51.64%)、FS组(37.19%)、RS组(31.60%)的抑瘤率。HE染色后镜下观察的结果也表明RPTN组对荷HCa-F细胞小鼠肝癌异位实体瘤抑制作用效果最好。结论:与RPN、RS和FS相比,在抑制荷HCa-F细胞小鼠肝癌异位移植实体瘤试验中RPTN具有良好的抗肿瘤作用。
[Abstract]:Objective: to investigate the heterlocation of vitamin E polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (RPTN) on HCa-F mice with high lymphoid metastasis of ascitic liver cancer in vivo. Inhibitory effect of implantable solid tumor. Methods: in order to ensure the safety of in vivo administration and determine the dosage, the half lethal dose (LD50) of RPTN and cinobufagin ligand solution (RS) in mice was investigated. The mice bearing HCa-F cells were divided into 6 groups: blank control group, blank nanoparticles group, 5-fluorouracil solution (FS) group and RS group. (RPN) group, RPTN group, tail vein administration, once a day, continuous administration for 7 days. On the day after withdrawal, the mice were sacrificed and the solid tumor volume was weighed and measured. According to the formula, the solid tumor volume growth and tumor inhibition rate were calculated. The solid tumor was fixed and embedded in paraffin section and observed by hematoxylin eosin (HE) staining to evaluate the antitumor effect of RPTN in mice. Results: the intravenous administration of LD50 in RPTN and RS mice was 38.2 mg kg-1 and 18.9 mg kg-1, respectively. the results showed that RPTN could reduce the toxicity of RBG in mice to a certain extent, which was safer than RS. After 7 days of antitumor test in mice, the volume growth of solid tumor in FS group, RPN group and RPTN group was significantly lower than that in blank control group (P 0.05 or P 0.01), RPTN group was 64.93%). The tumor inhibition rate of RPN group (51.64%), FS group (37.19%), RS group, 31.60%) was significantly higher than that of RPTN group (31.60%). The results of HE staining also showed that RPTN group had the best inhibitory effect on ectopic solid tumor of liver cancer in mice bearing HCa-F cells. Conclusion: compared with RPN,RS and FS, RPTN has a good antitumor effect in inhibiting the ectopic transplantation of liver cancer in mice bearing HCa-F cells.
【作者单位】：大连医科大学基础医学院;大连医科大学药学院;大连医科大学;
【基金】：辽宁省自然科学基金项目(编号:2015020308)
【分类号】：R965

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