靶向人fgl2的微小RNA腺病毒对裸鼠肝癌皮下瘤的抑制作用

Inhibitory effect of adenovirus-mediated microRNA targeting human fgl2 on subcutaneously implanted tumor of human hepatocellular carcinoma in nude mice

目的比较不同剂量的靶向人纤维介素蛋白(fibrinogen-like protein 2,fgl2)的微小RNA(micro RNA,miRNA)腺病毒注射液(Ad-hfgl2-miRNA)对裸鼠人肝癌皮下移植瘤生长的抑制作用。方法建立HCCLM3裸鼠人肝癌皮下移植瘤模型,瘤内注射高、中、低剂量(3.3×10^(10)IU、1.0×10^(10)IU、3.3×10~9IU)Ad-hfgl2-miRNA注射液及非相关对照(Ad-neg-miRNA),每6 d干预1次,共干预4次,期间测量肿瘤大小,计算相对肿瘤体积及相对肿瘤增殖率。结果各个干预组不同测量时间点的肿瘤体积均小于对照组,差异有统计学意义(P<0.05),且干预剂量越高,肿瘤生长的抑制作用更明显;高、中剂量干预组各时间点的相对肿瘤体积均显著小于对照组,差异有统计学意义(P<0.05),低剂量干预组和对照组比较差异无统计学意义。干预第16天和第19天时高、中、低剂量组相对肿瘤增殖率分别为28.37%、47.50%、57.65%及17.86%、44.50%、53.31%,抑制肿瘤生长效果明显。结论 Ad-hfgl2-miRNA腺病毒注射液显著抑制裸鼠人肝癌皮下瘤生长,干预效果明显,且干预效应和注射剂量有一定依赖关系,为探索肝癌生物治疗提供了新思路。

Objective To compare the inhibitory effect of adenovirus-mediated microRNA targeting human fibrinogenlike protein2（Ad-hfgl2-miRNA）with different doses on the growth of subcutaneously implanted tumor of human hepatocellular carcinoma in nude mice.Methods The subcutaneously transplanted tumor models of human hepatocellular carcinoma were established using HCCLM3.High-,medium-and low-dose（3.3×1010 IU,1.0×1010 IU,3.3×109 IU）of Ad-hfgl2-miRNA and unrelated control（Ad-neg-miRNA）were injected intratumorally once every 6 days for a total of 4 times.The sizes of the tumors were measured respectively on the day 1,3,5,7,10,13,16 and 19 during the intervention period and the relative tumor volumes and relative tumor proliferation rate were calculated.Results The average tumor volumes at different measurement time points in each intervention group were smaller than those in the control group（P〈0.05）,and the higher the intervention dose was,the more significant the inhibitory effect on tumor growth was.The relative tumor volumes at different measurement time points in high-and medium-dose intervention groups were significantly smaller than those in the control group（P〈0.05）.There was no significant difference in relative tumor volume between the low-dose intervention group and the control group.On the day 16 and 19 during the intervention period,the relative tumor inhibition rate in the high-,medium-and low-dose groups was 28.37%,47.50% and 57.65% as well as 17.86%,44.50% and 53.31%,respectively,and the inhibitory effect of Ad-hfgl2-miRNA on tumor growth was significant.Conclusions Ad-hfgl2-miRNA adenovirus significantly inhibits the growth of subcutaneously implanted tumor of human hepatocellular carcinoma in nude mice,and its intervention effect is obvious and dose-dependent.This study provides a new idea for exploring biological treatment of hepatocellular carcinoma.