IGF-1R硫代反义寡核苷酸抗人肝癌裸鼠原位移植瘤的研究

目的探讨IGF-1R硫代反义寡核苷酸（IGF-1R APSODN）对人肝癌裸鼠原位移植瘤的治疗效果及毒性作用。方法构建40只人肝癌裸鼠原位移植瘤模型，设溶剂对照组、IGF-1R APSODN（75，50，25mg／kg）三剂量组及氟尿嘧啶阳性对照组，各组裸鼠静脉给药25次，用药期间监测裸鼠体重变化，实验结束后行全血分析，肝肿瘤体积、重量测量，计算抑瘤率，病理组织学检查。重复实验一次。结果两次实验IGF-1R APSODN各剂量组肝肿瘤体积和重量均小于溶剂对照组，其中75mg／kg组抑瘤率分别为76．36％、71．81％，50mg／kg组抑瘤率分别为55．65％、61．74％，25mg／kg组抑瘤率分别为47．72％、50．34％。结论IGF-1R APSODN是一种高效、低毒的抗肝癌生物学药物。

Treatment of orthotopic implantation model of human hepatocellular carcinoma with IGF-1R antisense phosophorothioate oligodeoxynuclieotides in nude mice

Objective To investigate the therapeutic effect and side effect of IGF-1R antisense phosophorothioate oligodeoxynuclieotides (APSODN) on orthotopic implantation model of human hep-atocellular carcinoma (HCC) in nude mice. Methods Forty nude mice with orthotopically implanted human HCC were randomized into the NS control group, 3 IGF-1R APSODN groups of different doses and the 5-FU control group. The agents were given for 25 times through intravenous injection and the weight of nude mice measured in the course of treatment. When the experiment was over, the mouse blood cells were analyzed, volume and weight of the tumor measured, inhibitory rate of tumor growth calculated and pathomorphological changes examined. Then the whole course of experiment was repeated once. Results The average volume and weight of the tumor was significantly lower in the IGF-1R APSODN groups than in the NS control group (P<0. 05 or 0. 01). For the 2 experiments, the inhibitory rates of tumor growth were 76. 36% and 71. 81% in 75 mg/kg group, 55. 65% and 61. 74% in 50 mg/kg group and 47. 72% and 50. 34% in 25 mg/kg group, respectively. The weight of nude mice in each IGF-1R APSODN group was increased in the course of treatment. The average value of PLT was markedly lower in the 75 mg/kg group and 50 mg/kg group than in the NS control group (P <0. 05 or 0. 01) in the first experiment. Large pieces of necrosis and fibrosis with close dose-effect relationship could be seen under optical microscope in IGF-1R groups. Conclusions IGF-1R is a kind of anti-hepatoma biological agent with high efficiency and low side effect.