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[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。
[Objective] To investigate the effect of shRNA interfering fibroblast activating protein (FAP) expression on the growth of Lewis lung carcinoma in mice and to explore the possible mechanism. [Methods] Subcutaneous xenografts and lung metastases models of C57 female mice were established and randomly divided into 3 groups: FAP-shRNA group, HK group, 5% glucose group (5% GS), receiving FAP-shRNA interference plasmid liposome complex , Empty plasmid liposome complex and 5% glucose water treatment. Transplantation tumor size, weight, number of lung metastases and lung wet weight were recorded. The expression of FAP, the microvessel density and collagen fibers in each group were detected. [Results] The growth of subcutaneous xenografts in FAP-shRNA mice was slower than that in 5% GS and HK groups. The number of pulmonary metastases and the wet weight of lung in FAP-shRNA group were less than 5% GS and HK groups. And FAP-shRNA group FAP expression decreased, reduced microvessel density, increased expression of type I collagen, collagen deposition increased and the distribution of disorders. [Conclusion] The antitumor effect of FAP-shRNA interference plasmid may be achieved by reducing tumor angiogenesis, increasing type I collagen expression and finally changing tumor microenvironment.