白细胞介素-24对宫颈癌Hela细胞裸鼠移植瘤的生长和淋巴转移的抑制作用及其与肿瘤转移相关基因-1表达变化的关系

Inhibitory effect of interleukin-24 on cervical cancer hela cell transplant tumor growth and lymphatic metastasis and the correlation with metastasis associated-1 expression in nude mice

目的探讨基因重组质粒pDC316-hIL-24对裸鼠人宫颈癌移植瘤生长和淋巴转移抑制的作用,以及其与肿瘤转移相关基因(MTA-1)表达变化的关系。方法建立裸鼠人宫颈癌Hela细胞移植瘤动物模型,成瘤后动物模型随机分为3组,每组6只:磷酸盐缓冲液组(PBS组),空质粒组(B组),白细胞介素(IL)-24重组质粒组(C组)。期间观察并记录各组裸鼠移植瘤的生长情况及肿瘤体积和裸鼠体质量的变化,绘制生长曲线。实验结束后处死各组裸鼠,剥取瘤体并称重,同时寻找淋巴转移灶,计算肿瘤生长抑制率、转移率。应用反转录-聚合酶链反应(RT-PCR)法和免疫组织化学法检测移植瘤IL-24的转录水平以及MTA-1基因表达的变化。结果 基因重组质粒pDC316-hIL-24转染成功,各组的抑瘤率分别为A组:0,B组:4.3%,C组:46.5%。IL-24组抑瘤率与其余两组相比差异有统计学意义(P<0.01),其生命活动和体质量无明显异常。IL-24组的淋巴转移率较对照组和空质粒组有显著下降趋势。免疫组织化学显示C组MTA-1基因表达下调差异有统计学意义(P<0.01)。结论 IL-24干预宫颈癌荷瘤裸鼠与其他各组相比较,其抑制移植瘤生长的作用明显,淋巴转移率降低,且无毒副作用,对MTA-1有抑制作用。

Objective To investigate the inhibitory effect of gene recombinant plasmid pDC316-hIL-24 on transplant tumor growth and lymphatic metastasis in nude mice with human cervical cancer and the correlation with variation in metastasis associated-1 （MTA-1） expression. Methods Nude mice cervical cancer transplant tumor models were established and were randomly assigned into group A treated with phosphate buffer solution （n=6）, group B receiving empty plasmid injection （n=6） and group C subjected to recombinant plasmid pDC316-hIL-24 injection （n= 6）, respectively. Tumor growth and variation in the size and weight of nude mice were monitored during treatment for depicting growth plot. The nude mice were sacrificed at the end of trial, the tumors were removed and lymphatic metastatic foci were located for calculation of tumor growth inhibitory rate and metastasis rate. Transcription of IL -24 and variation in expression of MTA-1 in transplanted tumors were detected via real-time polymerase chain reaction and immunohistochemistry. Results Gene recombinant plasmid pDC316-hIL-24 was successfully transfected. The tumor inhibitory rate was 0 in group A, 4.3% in group B and 46.5% in group C, respectively. IL-24 was associated with markedly improved tumor inhibitory rate （P0.01） and significant decline in lymphatic metastasis rate （P0.01）, but not vital activity or body weight. The down-regulation of MTA-1 expression in group C reached statistical significance, as reflected by immunohistochemistry （P0.01）. Conclusion IL-24 confers dramatic inhibition on tumor growth and has resulted in reduced lymphatic metastasis rate in human cervical cancer nude mice model as compared with other groups. No adverse effect is found. These may be associated with attenuation of MTA-1 expression.