沉默黏着斑激酶表达抑制大肠癌转移的体内研究  

The effect of silenced focal adhesion kinase on colorectal cancer metastasis in vivo

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作  者:洪卫文[1] 苏国强[2] 应红安[3] 林峰[1] 梁卫东[1] 

机构地区:[1]台州市第一人民医院普外科,浙江台州318020 [2]厦门大学附属第一医院普外科,福建厦门361000 [3]台州市第一人民医院特需VIP科,浙江台州318020

出  处:《温州医学院学报》2015年第7期497-501,共5页Journal of Wenzhou Medical College

摘  要:目的:通过裸鼠实验研究,证实沉默黏着斑激酶(FAK)的表达能有效抑制大肠癌的转移。方法:将24只裸鼠随机分成3组:实验组、阴性对照组、未处理组,分别注射FAK稳定沉默的结肠癌细胞、阴性对照组的结肠癌细胞、未特殊处理的结肠癌细胞,每组各8只裸鼠。在SPF条件动物实验室饲养6周后处死裸鼠,观察原位成瘤率、病死率、瘤体生长、肝肺转移情况,通过HE染色、免疫组织化学染色研究FAK微转移灶、蛋白表达情况。结果:各组成瘤率均为100%。与阴性对照组及未处理组相比,实验组转移率、病死率和FAK蛋白表达明显降低(P<0.05),且转移灶恶变程度更低、形态更好,而阴性对照组与未处理组差异无统计学意义(P>0.05)。结论:通过sh RNA介导的FAK基因沉默对SW620原位移植后的裸鼠肝肺转移有明显抑制,FAK有望成为治疗大肠癌转移的新靶点。Objective: Focal adhesion kinase gene silencing by Short Hairpin RNA can effectively inhibit colorectal cancer’s metastasis were conifrmed through injection of FAK-knockdown colorectal cancer cells into nude mice.Methods: Twenty-four nude mice were randomly divided into three groups which were experimental group which inject FAK-knockdown colon cancer cells, negative control group whick inject negative control colon cancer cells and untreated group which inject untreated colon cancer cells. Nude mice were sacriifced after 6 weeks and tumor formation rate, mortality, tumor growth, liver and lung’s metastasis, miscrometastasis were observed and FAK protein expression were determined with HE staining and immunohistochemical staining. Results: Tumor formation rate was 100% in each group. Distant metastases, mortality and FAK protein expres-sion of experimental group was signiifcantly lower than that of the other two groups (P〈0.05), meanwhile, the malignant lesion extent was lighter. While negative control group and untreated group were not signiifcantly dif-ferent (P〉0.05).Conclusion: Lentiviral packaging shRNA-mediated FAK gene silencing can signiifcantly inhibit liver and lung metastasis of colorectal cancer. FAK is expected to be a new target for treatment of colon cancer metastasis.

关 键 词:黏着斑激酶 SW620 大肠肿瘤 裸鼠 转移 

分 类 号:R735.35[医药卫生—肿瘤]

 

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