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

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

Key words:  hepatocellular carcinoma  midkine antisense oligonucleotide  nano-liposomes  tumor inhibition rate

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。

Abstract:

OBJECTIVE To investigate the inhibition effect of midkine antisense oligodeoxynucleotides(Nano-MK-ASODN) 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.