鲜 爽,蔡 凡,王春婷.ShRNA干扰FAP蛋白表达对小鼠Lewis肺癌生长的影响[J].肿瘤学杂志,2014,20(10):781-786.
ShRNA干扰FAP蛋白表达对小鼠Lewis肺癌生长的影响
Influence of ShRNA Interference of Fibroblast Activation Protein (FAP) Expression on the Growth of Lewis Lung Cancer in Mice
投稿时间:2014-07-21  
DOI:10.11735/j.issn.1671-170X.2014.10.B001
中文关键词:  shRNA  成纤维细胞活化蛋白  肺肿瘤  微血管密度  胶原蛋白
英文关键词:shRNA  fibroblast activation protein(FAP)  lung neoplasms  microvessel density (MVD)  collage protein
基金项目:
作者单位
鲜 爽 四川大学华西医院 
蔡 凡 四川大学华西医院 
王春婷 四川大学生物治疗国家重点实验室 
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中文摘要:
      摘 要:[目的] 研究shRNA干扰成纤维细胞活化蛋白(FAP)表达对小鼠Lewis肺癌生长的影响并探讨可能的作用机制。[方法] 建立C57雌鼠皮下移植瘤和肺转移瘤模型,随机分成3组:FAP-shRNA组、HK组、5%葡萄糖(5%GS)组,分别接受FAP-shRNA干扰质粒脂质体复合物、空载质粒脂质体复合物及5%葡萄糖水治疗。记录移植瘤大小、重量,肺转移瘤数目及肺湿重。检测各组FAP表达水平、肿瘤微血管密度、胶原纤维情况。[结果] FAP-shRNA组小鼠皮下移植瘤生长较5%GS组和HK组缓慢。FAP-shRNA组的肺转移瘤结节数目和肺湿重均小于5%GS组和HK组。并且FAP-shRNA组FAP表达量下调,肿瘤微血管密度减少,Ⅰ型胶原蛋白表达增多,胶原纤维沉积增加且分布紊乱。[结论] FAP-shRNA干扰质粒抗肿瘤作用可能是通过减少肿瘤血管生成,增加Ⅰ型胶原蛋白表达,最终改变肿瘤微环境而实现的。
英文摘要:
      Abstrcat:[Purpose] To investigate influence of shRNA interference of fibroblast activation protein(FAP) expression on the growth of Lewis lung cancer in mice and its potential mechanism. [Methods] Female C57 mice received intravenous injection of Lewis lung cancer cells into tail vein or subcutaneous injection into right flank to establish lung metastasis model or subcutaneous xenograft model. In the two models,mice bearing Lewis lung cancer were randomly divided into three groups:FAP-shRNA group,HK group and 5%GS group,treated with FAP-shRNA,null-shRNA or 5% GS,respectively. Xenograft tumor size and weight,number of pulmonary metastatic nodules and lung weight were measured. FAP expression,microvessel density (MVD) and collagen fiber were evaluated.[Results]In subcutaneous xenograft model,FAP-shRNA group showed a significant reduction in tumor volume and tumor weight compared to 5%GS group and HK group(P<0.05). Moreover,number of pulmonary metastatic nodules and lung weight in FAP-shRNA group decreased significantly compared to 5%GS group and HK group(P<0.05). Compared to 5%GS group and HK group,FAP expression and MVD were lower in FAP-shRNA group,and type Ⅰ collagen protein increased with a perhaps increase in collagen fiber accumulation and derangements of collagen fiber.[Conclusion] The anti-tumor mechanism of FAP-shRNA interference plasmid is related to reduction of angiogenesis and increase in typeⅠcollage protein expresssion,which eventually change tumor microenvironment.
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