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目的:研究抗肝癌hdsFv-hEDN重组免疫毒素对荷人肝癌裸鼠皮下移植瘤生长的抑制作用,评价其作用为导向治疗药物的临床应用价值。方法:将体外培养的人肝癌细胞系SMMC-7721细胞接种于裸鼠皮下,建立荷人肝癌裸鼠皮下移植瘤动物模型,随机分为hdsFv-hEDN治疗组和对照组,分别给予尾静脉注射hdsFv-hEDN和生理盐水,1次/日,共2周。比较各组裸鼠皮下移植瘤生长速度、肿瘤体积和重量,并计算肿瘤的抑制率。取各组裸鼠肿瘤组织,心,肺,肝,肾组织HE染色,光学显微镜下观察。结果:抗肝癌hdsFv-hEDN治疗组裸鼠皮下移植瘤生长抑制作用显著,肿瘤生长速度减慢,肿瘤体积从42.62±0.57mm3增加到74.28±2.59mm3、瘤重为155.82±14.43mg,而对照组肿瘤体积从41.94±0.91mm3增加到127.42±4.81mm3、瘤重为283.28±15.21mg,两组比较差异非常显著。肿瘤体积抑瘤率和瘤重抑瘤率分别达到41.59±0.02%和45.51±0.09%。组织学观察抗肝癌hdsFv-hEDN组肿瘤组织出现大片坏死,凋亡明显增加,心、肝、肺、肾等重要器官未见明显异常。结论:抗肝癌hdsFv-hEDN重组免疫毒素对荷人肝癌裸鼠皮下移植瘤生长具有良好的抑制作用。
OBJECTIVE: To study the inhibitory effect of hdsFv-hEDN recombinant immunotoxin on the growth of subcutaneous xenografts in nude mice bearing human hepatocellular carcinoma and to evaluate its clinical value as a guideline therapeutic drug. Methods: Human hepatocellular carcinoma cell line SMMC-7721 was inoculated subcutaneously in nude mice to establish a subcutaneous xenograft tumor model of human hepatocellular carcinoma in nude mice. The cells were randomly divided into hdsFv-hEDN treatment group and control group. The hdsFv -hEDN and saline, 1 time / day, a total of 2 weeks. The growth rate, tumor volume and weight of subcutaneous xenografts in nude mice in each group were compared, and the tumor inhibition rate was calculated. Tumor tissue from each group of nude mice, heart, lung, liver and kidney were stained with HE and observed with light microscope. Results: The growth inhibitory effects of hdsFv-hEDN on the subcutaneous xenografts in nude mice were significant, the tumor growth slowed down, the tumor volume increased from 42.62 ± 0.57mm3 to 74.28 ± 2.59mm3, and the tumor weight was 155.82 ± 14.43mg, while the control group The tumor volume increased from 41.94 ± 0.91mm3 to 127.42 ± 4.81mm3, and the tumor weight was 283.28 ± 15.21mg, the difference between the two groups was significant. Tumor volume inhibition rate and tumor weight inhibition rate reached 41.59 ± 0.02% and 45.51 ± 0.09% respectively. Histopathological observation of hdsFv-hEDN group showed large necrosis of tumor tissue, apoptosis increased significantly, heart, liver, lung, kidney and other vital organs no significant abnormalities. Conclusion: The htdFv-hEDN recombinant immunotoxin against liver cancer has a good inhibitory effect on the growth of subcutaneous xenografts in nude mice bearing hepatocellular carcinoma.