慢病毒载体介导的CXCR7shRNA治疗人结肠癌皮下种植瘤的实验研究

目的探讨慢病毒载体介导的CXCR7-shRNA对人结肠癌裸鼠皮下种植瘤生长的抑制作用,为进一步研究以CXCR7为靶点的结肠癌基因治疗奠定基础。方法（1）构建CXCR7-shRNA慢病毒表达载体;（2）建立裸鼠人结肠癌荷瘤模型,计算成瘤率;（3）治疗组移植瘤内注射慢病毒CXCR7-shRNA表达载体并建立阴性对照（注射慢病毒shRNA阴性对照）和空白对照（注射PPS）,测量肿瘤体积和动物体质量,计算肿瘤抑制率。结果将HT-29细胞移植到裸鼠背部皮下,成瘤率为100.0%;治疗组裸鼠的肿瘤体积较阴性对照组和空白对照显著缩小（P〈0.05）、动物体质量显著增加（P〈0.05）、肿瘤抑制率分别为38.0%和34.0%。结论CXCR7-shRNA慢病毒表达载体能显著抑制人结肠癌裸鼠移植瘤的生长;针对CXCR7基因序列设计的siRNA可作为具有开发前途的抗肿瘤新药,其在体实验中CXCR7的作用机制尚需进一步深入探讨。

Study on treatment of subcutaneous implantation tumor of human colon cancer using lentiviral vector-mediated CXCR7-shRNA

Objective To investigate the inhibitory effect of lentiviral vector-mediated CXCR7-siRNA on subcutaneous xenograft of human colon cancer in nude mice,enlightening further study of CXCR7-targeting gene treatment. Methods （1） CXCR7-shRNA lentiviral expressive vector was constructed. （2）The model of bearing-tumor of human colon cancer in nude mice was established and the tumor-formation rate calculated. （3）The treatment group,negative control group and blank control group were given injection of lentiviral-CXCR7shRNA, lentiviral-shRNA and PPS into subcutaneous xenograft, respectively. Tumor volume,tumor-growth-inhibition rate and animal weight were measured,respectively. Results Tumors implanted were established successfully by 100.0% with HT-29 cells. Compared with negative control and blank control groups,the treatment group using lentiviral CXCRT-siRNA could significantly decrease tumor volume （P〈0.05） and increase body weight （P〈0.05） with 38.0% and 34.0% of tumor-growth-inhibition ratio,respectively. Conclusions The lentiviral-CXCRTshRNA can effectively inhibit implanted tumor growth in human colon cancer-bearing nude mice. siRNA of CXCRT- targeting can be used as the highly promising anti-tumor drug,which requires further study on mechanism of CXCR7 action in vivo.