重组凋亡素对人卵巢癌裸鼠移植瘤生长抑制作用的影响

Inhibitory growth effect of recombinant apoptin on human ovarian cancer xenografts in nude mouse model

目的观察凋亡素(VP3)基因真核表达质粒对人卵巢癌裸鼠异种移植瘤生长的抑制作用。方法建立人卵巢癌(COC1)细胞裸鼠异种移植瘤模型。实验裸鼠分为四组:高剂量实验组(pcDNA-VP3质粒DNA,瘤内注射,100μg/只);低剂量实验组(pcDNA-VP3质粒DNA,瘤内注射,50μg/只);空载体对照组[pcDNA3.1(+)质粒DNA,瘤内注射,100μg/只];脂质体对照组(脂质体,瘤内注射,0.2mL/只)。每3d测量皮下移植瘤长、宽径,按标准公式V=L×W2×0.52计算移植瘤体积。12天后处死裸鼠,称取瘤重。使用TUNEL法观察凋亡素对皮下移植瘤细胞凋亡程度的影响。结果pcDNA-VP3高剂量组和低剂量组卵巢癌裸鼠皮下移植瘤生长明显受抑制,高剂量组和低剂量组肿瘤生长抑制率分别为76%和52%;瘤重抑制率分别为71.9%和49.5%(P<0.05)。TUNEL实验结果表明凋亡素在体内以凋亡方式诱导肿瘤细胞死亡。结论重组凋亡素基因真核表达质粒具有抑制人卵巢癌裸鼠异种移植瘤生长作用。凋亡素在瘤组织中以诱导凋亡方式抑制卵巢癌裸鼠异种移植瘤生长。

[Objective] To investigate the inhibitory growth effect of recombinant apoptin eukaryotie expreession plasmid on human ovarian cancer xenografts in nude mouse model. [Methods] Approximate 2×10^6 cells of ovarian cancer cells （COC1） were implanted subcutaneously into per nude mouse. Twelve female Balb/e nude mice were divided into as follow four groups： high doesage group and low doseage group were received intratumoral injection at does of 100 μg and 50μg peDNA-VP3 plasmid eDNA respectively. Plasmid control group and lipofeetamine control group were received injection at does of 100 μg peDNA 3.1 （＋） eDNA and the same volume of liprofectamine. The length and wideth of the xenograft tumor were mearsured every three days, eaeulate the volume of the tumor aeeoding to the formula ： V=L×W^2×0.52. These mice were sacrificed after twelve days, and their tumors were excised. The mean tumor weight per group were caculated. Apoptosis of the xenograft tumor was observed by TUNLE assay analysis. [Results] The tumor growth inhibitory rate of high dose of pcDNA-VP3 group and low dose of pcDNA-VP3 group were 76%, 52% respectively （P 〈0.05）; The tumor weight inhibitory rate were 71.9% and 49.5% respectively （P 〈0.05）. [Conclusion] Recombinant eukaryofic expression plasmid pcDNA-VP3 by intratumoral injected could inhibit the growth of humane ovarian cancer xenograft tumor in nude mouse; Apoptin inhibits growth of xenograft tumor via induction of aoootosis in nude mice.