Antisense oligonucleotide against insulin-like growth factor I receptor inhibits tumor growth in human hepatocellular carcinoma orthotopic implantation models and its influence on the blood indicators in nude mice in vivo

Objective To investigate the inhibitory effect of antisense oligonucleotide against insulin-like growth factor 1 receptor (IGR-1R) on tumor growth in human hepatocellular carcinoma orthotopic implantation models and its influence on the blood indicators in nude mice. Methods We did the experiment 3 times, and 40 models for each time were divided into 5 groups randomly: NS control group, three IGF-1R antisense oligdeoxynucleotides (ASODN) [75, 50, 25 mg/(kg·day)] groups and 5-fluorouracil (5-Fu) control group. Eighty nude mice served as normal control group. The agents were given for 25 times through intravenous injection in human hepatocellular carcinoma orthotopic implantation models. When the experiment was over, the volume and weight of tumor were measure, the inhibitory rate of tumor growth was calculate, and the pathomorphological change was examined. Alpha fetal protein (AFP), routine blood test and biochemical indexes were determined in three experiments respectively. Results The average volume and weight of tumor in IGF-1R ASODN group was significantly reduced as compared with those in NS control group. The inhibitory rate of tumor growth in 75 mg/(kg·day) IGF-1R APSODN group in three experiments were 76.36%, 71.81% and 78.81%, 55.65%, 61.74% and 63.58% in 50 mg/(kg·day) group, and 47.72%, 50.34% and 54.30% in 25 mg/(kg·day) group respectively. Large piece of necrosis and fibrosis could be seen under a light microscope in IGF-1R ASODN groups. AFP in IGF-1R ASODN groups was lower (P<0.05) than in NS control group, PLT in IGF-1R ASODN group [75 mg/(kg·day)] was lower than in NS control group (P<0.05), and GLU in IGF-1R ASODN group [75 mg/(kg·day) and 50 mg/(kg·day)] was higher than in normal control group (P<0.05). There was no significant difference between IGF-1R ASODN group and normal control group in other blood indicators. Conclusion IGF-1R ASODN is an anti-hepatoma biological agent with high efficiency and low side-effect. Key words: Carcinoma, hepatocellular; Insulin-like growth factor 1 receptor; Antisense oligdeoxynucleotides; Inhibitory rates of tumor growth