【摘 要】
：
目的 研究瘤内注射慢病毒载体介导的NK4过表达对肺腺癌移植瘤生长、远处转移以及微血管生成的影响.方法 构建人肺腺癌A549裸鼠皮下移植瘤模型并按照随机数字表法分为磷酸盐缓冲液(PBS)组、LV-con组和LV-NK4组,每组5只.通过瘤内注射的方式分别向3组注射PBS(25μL)、阴性对照慢病毒载体LV-con(25μL,6×108 TU/mL)和重组过表达慢病毒载体LV-NK4(25μL,6×108 TU/mL),共注射2次,间隔3 d.观察裸鼠皮下移植瘤生长情况,测量瘤体积、瘤质量,计算抑瘤率.HE染
【机 构】
：
南京医科大学附属常州市第二人民医院呼吸与危重症医学科 213000
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目的 研究瘤内注射慢病毒载体介导的NK4过表达对肺腺癌移植瘤生长、远处转移以及微血管生成的影响.方法 构建人肺腺癌A549裸鼠皮下移植瘤模型并按照随机数字表法分为磷酸盐缓冲液(PBS)组、LV-con组和LV-NK4组,每组5只.通过瘤内注射的方式分别向3组注射PBS(25μL)、阴性对照慢病毒载体LV-con(25μL,6×108 TU/mL)和重组过表达慢病毒载体LV-NK4(25μL,6×108 TU/mL),共注射2次,间隔3 d.观察裸鼠皮下移植瘤生长情况,测量瘤体积、瘤质量,计算抑瘤率.HE染色观察肿瘤组织和肺组织的形态变化.免疫组化染色检测c-Met、CD31表达,微血管密度(MVD)检测评估肿瘤血管生成情况.原位缺口末端标记(TUNEL)法检测瘤组织细胞凋亡情况.实时荧光定量聚合酶链反应(qPCR)和Western blot分别检测NK4 mRNA及蛋白表达水平.结果 成功构建裸鼠肺腺癌移植瘤模型.小鼠荷瘤实验显示,LV-NK4组瘤体积、瘤质量均小于LV-con组和PBS组(P<0.05),而LV-con组和PBS组间差异无统计学意义.LV-NK4组抑瘤率为44.51％,LV-con组抑瘤率为10.35％.LV-NK4组肿瘤组织凋亡、坏死明显增多,c-Met蛋白表达量减少,微血管生成受到抑制.肺组织HE染色结果发现,LV-con组和PBS组可见肿瘤转移灶,LV-NK4组未见明显转移灶.LV-NK4组NK4 mRNA及蛋白表达水平均高于LV-con组和PBS组.结论 慢病毒介导的NK4过表达可以通过抑制c-Met蛋白表达及微血管的形成,抑制裸鼠肺腺癌移植瘤的生长和肺部转移.
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