Nano-MK-ASODN对人肝癌裸鼠原位移植模型的影响  

Effect of Nano-MK-ASODN in Orthotopic Implantation of Human Hepatocellular Carcinoma

作　　者：申屠琳慧 韩奇[1] 周林福[2] 任艳丽 李杨霞 戴利成[3] SHENTU Linhui;HAN Qi;ZHOU Linfu;REN Yanli;LI Yangxia;DAI Licheng(Department of Pharmacy,Zhejiang Hospital,Hangzhou 310012,China;Department of Basic Medicine,School of Medicine,Zhejiang University,Hangzhou 310058,China;Central Laboratory,Huzhou Central Hospital,Huzhou 313003,China)

机构地区：[1]浙江医院药剂科,杭州310012 [2]浙江大学医学院基础医学系,杭州310058 [3]湖州市中心医院中心实验室,浙江湖州313003

出　　处：《中国现代应用药学》2019年第24期3014-3018,共5页Chinese Journal of Modern Applied Pharmacy

基　　金：“重大新药创制”国家科技重大专项(2013ZX09102051)

摘　　要：目的探讨中期因子反义寡核苷酸纳米脂质体(Nano-MK-ASODN)对人肝癌裸鼠原位移植模型的抑制作用。方法利用人肝癌裸鼠原位移植模型,建模后待肿瘤长到一定体积时进行分组,分为溶剂对照组、空脂质体对照组、无义ASODN组、MK-ASODN 25,12.5,6.25 mg·kg?1组、Nano-MK-ASODN 25,12.5,6.25 mg·kg?1组,同时再选取正常裸鼠作为正常裸鼠对照组。观察受试药品中期因子反义寡核苷酸(MK-ASODN)和Nano-MK-ASODN对荷瘤裸鼠体质量、瘤重以及肿瘤生长的抑制率的影响。检测荷瘤裸鼠外周血指标和血浆甲胎蛋白(alpha fetoprotein,AFP)的水平。结果MK-ASODN 25,12.5,6.25 mg·kg?1组的肿瘤抑制率分别为53.72%,48.76%,42.98%,Nano-MK-ASODN 25,12.5,6.25 mg·kg?1组肿瘤抑制率分别为66.94%,56.20%,52.07%,各组肿瘤质量与溶剂对照组比较均有显著差异(P<0.05)。Nano-MK-ASODN组肿瘤质量以及AFP水平明显小于溶剂对照组(P<0.05)。Nano-MK-ASODN各剂量组在用药后体质量、外周血血常规与空脂质体对照组、无义ASODN组以及正常裸鼠对照组比较,差异均无统计学意义。病理组织学检查显示,Nano-MK-ASODN治疗组荷瘤裸鼠的肝内肿瘤体积缩小,并可见液化,能使部分肝癌细胞变性坏死。结论Nano-MK-ASODN对人肝癌裸鼠原位移植瘤具有显著的抑制作用,且效果显著强于MK-ASODN。OBJECTIVE To investigate the inhibition effect of midkine antisense oligodeoxynucleotides(Nano-MKASODN)on the orthotopic transplantation model of human hepatocellular carcinoma in nude mice.METHODS Nude mice with model of human hepatocellular carcinoma were divided into solvent control group,liposome control group,nonsense-ASODN control,25,12.5 and 6.25 mg·kg?1 of MK-ASODN group,25,12.5 and 6.25 mg·kg?1 of Nano-MK-ASODN group.Normal nude mice were selected as normal control group.Weight,tumor weight,tumor growth inhibition rate,blood routine and AFP of nude mice were detected.RESULTS The tumor suppression rates of MK-ASODN 25,12.5,6.25 mg·kg?1 group were 53.72%,48.76%,42.98%,the tumor suppression rates of Nano-MK-ASODN 25,12.5,6.25 mg·kg?1 were 66.94%,56.20%,and 52.07%.The tumor quality of each group was significantly different from that of the solvent control group(P<0.05).The tumor mass and AFP level in the Nano-MK-ASODN group were significantly lower than those in the solvent control group(P<0.05).There was no significant difference in the body weight,peripheral blood routine,between Nano-MK-ASODN group and liposome control group,nonsense-ASODN control or normal control group.At the same time,anatomical and histopathological examination showed that the volume of liver tumor in Nano-MK-ASODN treated group was reduced and liquefied,which could cause degeneration and necrosis of some hepatocellular carcinoma cells.CONCLUSION Nano-MK-ASODN could significantly inhibit human hepatocellular carcinoma orthotopic transplantation in nude mice,and the effect was significantly stronger than that of MK-ASODN.

关 键 词：肝癌 中期因子反义寡核苷酸 纳米脂质体 肿瘤抑制率 

分 类 号：R965.2[医药卫生—药理学]