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靶向β-catenin短发夹RNA抑制人结肠癌裸鼠移植瘤的实验研究

Inhibitory effect of β-catenin short hairpin RNA on the growth of human colon cancer xenografts in nude mice
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摘要 目的探讨靶向β-catenin的短发夹RNA(shRNA)对人结肠癌裸鼠移植瘤的生长抑制作⒚。方法构建两个靶向β-catenin的短发夹RNA的质粒载体CAT1、CAT2和阴性对照质粒Neg,并将其Κ入人结肠癌Colo205细胞,分组种植到裸鼠皮下以建立人结肠癌裸鼠移植瘤模型。随后观察监测各组裸鼠的肿瘤生长情况。第8周裸鼠处死并剥离出肿瘤组织,HE染色观察肿瘤细胞的形态,免疫组化方法检测β-catenin蛋白的表达,TUNEL法检测肿瘤细胞的凋亡情况。结果各组裸鼠的内脏未受到明显的毒害和损伤。第8周CAT1、CAT2实验组裸鼠移植瘤的体积和质量与空白对照组相比均有显著性缩小(P<0.05),抑制率大约在50%左右。而且与空白对照组相比,CAT1、CAT2组移植瘤的β-catenin表达均有显著性下调,肿瘤细胞凋亡指数均有显著性的升高(P<0.05)。阴性对照组的上述指标与空白对照组相比差异均无统计学意义。结论所构建的靶向β-catenin的短发夹shRNA能够抑制人结肠癌Co-lo205细胞裸鼠移植瘤的生长,为结肠癌基因治疗开辟新的思路。 Objective To investigate the effect of β -catenin short hairpin RNA(shRNA) on the growth of human colon cancer xenografts in nude mice. Methods Two plasmid vectors of β-catenin shRNA(CAT1 and CAT2) were constructed and transfected into human colon cancer cell line Colo205. These cells were transplanted into nude mice to establish cancer xenograft. Tumor growth was monitored. Tumor morphology was observed by HE staining. The expression of β-catenin protein in tumor tissue was detected by immunohistochemistly. Cell apoptosis was detected by TUNEL assay. Results No obvious damage of the internal organs was found in these nude mice. On the eighth week compared with the blank control groups, the tumor volume and weight were both significantly smaller in the two experimental groups(CAT1 and CAT2 group). The inhibition rates were about 50%. Furthermore, the β -catenin expression index were significantly lower and the apoptosis index of tumor cells were significantly higher in these two experimental groups(P 〈0.05). No significant difference was found between the negative control and blank control groups. Conclusions β -catenin shRNA can inhibit the growth of human colon cancer xenograft in nude mice, which provide a new way for the conlon cancer gene theraphy.
出处 《中华普通外科学文献(电子版)》 2009年第6期9-11,共3页 Chinese Archives of General Surgery(Electronic Edition)
基金 广东省科技厅科技计划资助项目(2007B030702012)
关键词 RNA干扰 结肠癌 裸小鼠 β—catenin 移植瘤 RNA interference Colon cancer , Nude mice β -catenin Xenograft
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