Nano-MK-ASODN对人肝癌裸鼠原位移植模型的影响

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，观察受试药品中期因子反义寡核苷酸（MK-ASODN）和Nano-MK-ASODN对荷瘤裸鼠体重、瘤重、以及肿瘤生长的抑制率的影响。检测荷瘤裸鼠血常规和血浆甲胎蛋白水平。结果 MK-ASODN高剂量组25 mg.kg-1组的瘤重抑制率为53.72%，12.5 mg.kg-1组的瘤重抑制率为48.76%，6.25 mg.kg-1组的瘤重抑制率为42.98%，Nano-MK-ASODN 25 mg.kg-1剂量组抑制率为66.94%，12.5 mg.kg-1组的瘤重抑制率为56.20%，6.25 mg.kg-1组的瘤重抑制率为52.07%，所有试验组肿瘤重量与溶剂对照组比较均有显著差异，P<0.01。Nano-MK-ASODN组肿瘤重量明显小于同等剂量MK-ASODN，P<0.01。Nano-MK-ASODN治疗组肿瘤体积以及AFP水平明显小于对照组，P<0.01。治疗组瘤重明显小于生理盐水对照组，P<0.05。Nano-MK-ASODN各治疗组及用药后体重、血常规与对照组比较指标差异均无显著性意义，P>0.05。同时，解剖学和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。

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

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 The orthotopic transplantation models of human hepatocellular carcinoma in nude mice were used to observe the effects of MK-ASODN and Nano-MK-ASODN respectively. Weight, tumor weight, tumor growth inhibition rate, blood routine and AFP of nude mice were detected. Results Both MK-ASODN and Nano-MK-ASODN could significantly inhibit orthotopic implantation of human hepatocellular carcinoma proliferation dose-dependently (P< 0.01): 25 mg.kg-1 of MK-ASODN with 53.72% inhibition rate; 12.5 mg.kg-1 of MK-ASODN with 48.76% inhibition rate; 6.25 mg.kg-1 of Nano-MK-ASODN with 42.98% inhibition rate; 25 mg.kg-1 of Nano-MK-ASODN with 66.94% inhibition rate.12.5 mg.kg-1 of Nano-MK-ASODN with 56.20% inhibition rate; 6.25 mg.kg-1 of Nano-MK-ASODN with 52.07% inhibition rate. There was no significant difference in the indexes of weight, blood routine within the control groups and experiment groups, P>0.05. 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.