细丝蛋白A抑制荷人结肠腺癌细胞SW480裸鼠移植瘤的生长  

Inhibitory effect of filamin A on tumor formation activity of human colon carcinoma SW480 cells in nude mice

作　　者：史建伟[1,2] 于跃明[2] 王士杰[3] 王小玲[4] 王贵英[2] 

机构地区：[1]河北大学附属医院肿瘤外科,保定071000 [2]河北医科大学第四医院外科,石家庄050011 [3]河北医科大学第四医院内镜室,石家庄050011 [4]河北医科大学第四医院病理科,石家庄050011

出　　处：《肿瘤》2011年第8期701-706,共6页Tumor

基　　金：河北省卫生厅医学科学研究重点课题(编号:20090010);河北省教育厅高校强势特色学科建设基金[编号:冀高教(2005)52号]

摘　　要：目的:探讨细丝蛋白A(fi lamin A,FLNa)基因对人结肠腺癌SW480细胞在裸鼠体内成瘤的影响及其可能的机制。方法:将重组载体质粒pcDNA3.1/V5-His-TOPO/FLNa通过脂质体介导的方式转染到SW480细胞中,RT-PCR和蛋白质印迹法检测SW480/FLNa细胞中FLNa mRNA和蛋白的表达,MTT法检测细胞的体外增殖能力。将SW480/FLNa、SW480/pcDNA3.1和SW480细胞接种于裸鼠皮下,观察移植瘤的生长情况,计算抑瘤率,HE染色观察移植瘤组织的形态学变化,RT-PCR和蛋白质印迹法检测移植瘤组织中基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)mRNA和蛋白的表达水平。结果:FLNa基因在SW480细胞中获得稳定表达,SW480/FLNa、SW480/pcDNA3.1和SW480细胞的体外增殖能力相似;SW480/FLNa组移植瘤的生长速度和质量低于SW480组,抑瘤率为(88.7±3.5)%(P=0.000);SW480/FLNa组移植瘤组织出现退变坏死,MMP-9mRNA和蛋白的表达水平(0.11±0.02和0.02±0.00)均低于SW480组(1.12±0.02和1.25±0.05),差异均有统计学意义(P=0.012,P=0.025)。结论:FLNa基因具有抑制人结肠腺癌SW480细胞在裸鼠体内的生长作用,其作用机制可能与下调MMP-9的表达有关。Objective： To explore the effect of filamin A （FLNa） gene on tumor formation activity of human colon carcinoma SW480 cells in nude mice and to elucidate the possible mechanism. Methods： Recombinant vector plasmid of pcDNA3.1/V5-His-TOPO/FLNa was transfected into SW480 cells by lipofectAMINE. The expression levels of FLNa mRNA and protein in SW480/FLNa cells were detected by RT-PCR and Western blotting. The proliferation rate of SW480/FLNa cells was determined by MTT assay. The SW480/FLNa, SW480/pcDNA3.1 and SW480 cells were subcutaneously injected into nude mice. The xenograft tumor growth was observed. The inhibitory rate of tumor was calculated. The morphology of tumor was observed under an optical microscope. The expression levels of matrix metalloproteinase-9 （MMP-9） mRNA and protein in xenograft tumor tissues were determined by RT-PCR and Western blotting. Results： FLNa gene was stably expressed in SW480 cells. The proliferation abilities of SW480/FLNa, SW480/pcDNA3.1 and SW480 cells were similar in vitro. The growth rate and the weight of tumor in the SW480/FLNa group were both lower than those in the SW480 group （P=0.000）. The inhibition rate of tumor in the SW480/FLNa group was （88.7±3.5）%. Degeneration and necrosis were found in tumor tissues of SW480/FLNa group. The expression levels of MMP-9 mRNA （0.11±0.02） and protein （0.02±0.00） were both lower in the SW480/FLNa group than those in the SW480 group （1.12±0.02 and 1.25±0.05, respectively）, and there were significant differences （P=0.012,P=0.025）. Conclusion： FLNa gene may inhibit the tumor formation activity of human colon carcinoma SW480 cells in nude mice. This effect may be associated with down-regulation of MMP-9 expression.

关 键 词：结直肠肿瘤 小鼠 裸 基因 肿瘤抑制 细丝蛋白A 细胞 SW480 

分 类 号：R735.3[医药卫生—肿瘤]