人内皮抑素转基因治疗裸鼠人大肠癌

Anti-tumor effect through human endostatin gene transfer in nude mice-bearing human colorectal cancer

目的 研究瘤内注射携带人内皮抑素 (hEN)基因的SA脂质体对裸鼠体内大肠癌LoVo细胞生长的抑制作用。方法 克隆、修饰hEN并构建真核表达质粒pcDNA3 hEN ,2 0 μg质粒加 40 μgSA脂质体构建SA pcDNA3hEN。 3 2只裸鼠背部皮下注射 2× 10 5/mlLoVo细胞悬液建立人大肠癌裸鼠模型。随机分 4组分别瘤内注射NS、SA、SA pcDNA3和SA pcDNA3hEN后 4、8、12、16d测量肿瘤体积。结果 SA pcDNA3hEN组肿瘤平均体积均小于对照组 ,第 12、16天的平均体积分别为 (0 .2 7± 0 .2 1)cm3 及 (0 .5 7± 0 .41)cm3 ,而对照组肿瘤体积为 :NS组 (0 .89± 0 .3 9)cm3及 (2 .5 0± 0 .91)cm3 ;SA组 :(0 .98± 0 .69)cm3 及 (1.98± 0 .5 9)cm3 ;SA pcDNA3组 :(0 .90± 0 .3 4)cm3 及 (1.88± 1.0 2 )cm3 ,差异有显著性 (P <0 .0 5 )。结论 瘤内注射携带hEN基因的SA脂质体可抑制裸鼠体内种植性人大肠癌的生长。

Objective To investigate the inhibitory effects of in vivo directly administered SA liposome packed eukaryotic expression plasmid carrying human endostatin (hEN) on the growth of human colorectal cancer implanted in nude mice.Methods The hEN gene sequence was cloned and modified.Eukaryotic expression plasmid containing hEN gene: pcDNA3 hEN was constructed.20?μg plasmid was packed with 40?μg SA liposome to construct SA pcDNA3?hEN.Then SA pcDNA3hEN was injected directly into human colorectal cancer established by intra cutaneous injection of 2×10 5/ml?LoVo cell suspension in 32 nude mice.Then these mice were randomly divided into 4 groups which were subjected to the injection of NS,SA,SA pcDNA3 and SA pcDNA3?hEN respectively.After injection the tumor size was examined on the 4th,8th,12th,and 16th day.Results The average tumor size of group SA pcDNA3?hEN was smaller than in the control group.Especially on the 12th and 16th days,the average tumor size in the group SA pcDNA3?hEN was (0.27±0.21)?cm 3 and (0.57±0.41)?cm 3 respectively,presenting significantly statistical difference (P<0.05) as compared with NS group (0.89±0.39)?cm 3 and (2.50±0.91)?cm 3,SA group (0.98±0.69)?cm 3 and (1.98±0.59)?cm 3 and SA pcDNA3 group (0.90±0.34)?cm 3 and (1.88±1.02)?cm 3.Conclusion The direct injection of eukaryotic expression plasmid pcDNA3hEN carrying hEN gene via SA liposome packaging inhibits the growth of LoVo colorectal cancer.