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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(H&E)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(P<0.05或P<0.01),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。H&E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。
OBJECTIVE: To investigate the effect of RPGA on the lymphatic metastasis of hepatocellular carcinoma with asparagine -F mouse xenograft solid tumor inhibition. Methods: In order to ensure the safety of administration in vivo and to determine the dose, the LD50 of RPTN and RSV in mice were determined. The model of xenograft hepatocellular carcinoma in HCa-F mice was established and divided into 6 groups: blank control group, blank nanoparticle group, 5-fluorouracil solution (FS) group, RS group, PLGA nanoparticles (RPN) group, RPTN group and tail vein were administered once a day for 7 days. After the mice were sacrificed the following day, the solid tumors were dissected The volume of solid tumors was measured and the volumes of solid tumors were measured according to the formula. The solid tumors were fixed and embedded in paraffin sections and stained with hematoxylin & eosin (H & E) for comprehensive evaluation of RPTN in mice Anti-tumor effect. Results: The LD50 of RPTN and RS mice was 38.2 mg · kg-1 and 18.9 mg · kg-1, respectively, indicating that RPTN can reduce the toxic effect of RBG in mice to some extent and is safer than RS. The volume of solid tumor growth in FS group, RPN group and RPTN group decreased significantly (P <0.05 or P <0.01) after 7 d administration in anti-tumor in mice, The rate was 64.93%, which was significantly higher than that of RPN group (51.64%), FS group (37.19%) and RS group (31.60%). The results of microscopic observation after H & E staining also showed that RPTN group had the best inhibitory effect on ectopic solid tumor of liver cancer in HCa-F mice. Conclusion: Compared with RPN, RS and FS, RPTN has a good anti-tumor effect in the inhibition of HCa-F-bearing mice xenografts in liver cancer xenografts.