特异性靶向Bcl-XL ShRNA抑制Lovo细胞移植瘤生长的实验研究

Bcl-XL shRNA inhibited the growth of colon cancer Lovo cells' xenografts in nude mice

目的探讨靶向Bcl-XL shRNA对人结肠癌Lovo细胞裸鼠移植瘤的生长抑制作用。方法构建两个靶向Bcl-XL的shRNA质粒载体XL1、XL2和阴性对照质粒Neg,并将其转入人结肠癌Lovo细胞,分组种植建立人结肠癌裸鼠移植瘤模型。随后观察各组裸鼠的肿瘤生长情况。第8周裸鼠处死,HE染色观察肿瘤细胞的形态,免疫组化方法检测Bcl-XL蛋白的表达,TUNEL法检测肿瘤细胞的凋亡情况。结果第8周XL1、XL2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缩小(P<0.05),抑制率约50%。与空白对照组相比,XL1、XL2组移植瘤的Bcl-XL表达均有显著下调,肿瘤细胞凋亡指数均有显著升高(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。结论靶向Bcl-XL shRNA能够抑制人结肠癌Lovo细胞裸鼠移植瘤的生长,可能机制为促进肿瘤细胞凋亡。

Objective To investigate the effect of Bcl-XL short hairpin RNA(shRNA) on the growth of human colon cancer xenografts in nude mice.Methods Two plasmid vectors of Bcl-XL shRNA(XL1 and XL2) were constructed and transfected into human colon cancer cell line Lovo.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 Bcl-XL protein in tumor tissue was detected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.Results On the eighth week,the tumor volume and weight were both significantly smaller in two experimental groups (XL1 and XL2 group) compared with those in the blank control group.The inhibition rates were about 50%.Furthermore,the Bcl-XL expression rate were significantly lower and the apoptosis rate of tumor cells were significantly higher in these two experimental groups (P<0.05).No significant differences were found between the negative control and blank control groups.Conclusion Bcl-XL shRNA can inhibit the growth of human colon cancer xenograft in nude mice,which may promote apoptosis of tumor cells.