靶向抑制皮层肌动蛋白与Arp2/3复合物结合对结肠癌侵袭和转移的抑制作用  

Target Inhibiting the Binding of Cortactin and Arp2/3 Complex Supresses the Invasion and Metastasis of Colon Carcinoma

作　　者：吴寒[1] 袁岱岳[2] 贾晓斌[1] 钱飞[1] 朱建伟[1] 

机构地区：[1]南通大学附属医院普外科,江苏南通226001 [2]江苏省南通市第一人民医院普外科,江苏南通226001

出　　处：《中国临床医学》2012年第6期591-593,共3页Chinese Journal of Clinical Medicine

基　　金：国家自然科学基金资助项目(编号:30771126);江苏省自然科学基金资助项目(编号:BK2006058)

摘　　要：目的:探讨靶向抑制皮层肌动蛋白(cortactin)与Arp2/3复合物结合对结肠癌细胞株LoVo侵袭与转移的抑制作用。方法:根据cortactin与Arp2/3复合物相互结合的各功能区,构建仅包含cortactin与肌动蛋白结合的ABR重复序列区域,但无氨基末端酸性区域(NTA)的重组cortactin质粒(EGFP/N2/ABR,ABR质粒);并将其转染高侵袭性人大肠癌细胞株LoVo。建立裸鼠结肠癌肝转移模型,并将其分为未转染重组质粒组(LoVo组)、转染空质粒组和转染重组质粒组(EGFP/N2/ABR组)。在裸鼠脾包膜下注射转染相应类型质粒的LoVo细胞株。比较各组间肝转移结节的数量、大小、分布的差异。观察半乳糖凝集素(galectin-1)蛋白在各组转移结节中的表达。结果:EGFP/N2/ABR组肝脏转移肿瘤结节的大小和数量与LoVo组相比均显著减少(P<0.05)。EGFP/N2/ABR组中galectin-1蛋白表达较LoVo组显著下降(P<0.05)。结论:阻断cortactin与Arp2/3复合物的结合可抑制结肠癌的体内转移,这可能与其下调galectin-1表达有关。Objective：To evaluate the influence of inhibition of the binding of cortactin and Arp2/3 complex on the invasion and metastasis of colon cancer. Methods： According to the binding domain of cortactin and Arp2/3 complex, the recombinant plas- mid（ABR plasmid）was successfully constructed,which contained ABR domain, but without NTA domain. Then ABR plasmid wastransfected into colorectal cancer cell line LoVo. A mouse model of metastatic colon cancer was constructed by injection of LoVo cell line into spleen of mice. Mice were divided into three groups： LoVo group, mice in which were not transfected with the recombinant plasrnid; control group, mice in which were transfected with empty plasmid; and the recombinant plasmid transfected group （EGFP/N2/ABR group）. Differences in the number, size, and distribution of liver metastatic nodules were compared among the 3 groups. Expression level of galectin-I was detected. Results： The size and number of metastatic tumors in liver of EGFP/N2/ABR group were significantly smaller than those in LoVo group（P〈0.05）. The expression of galectin-1 in EGFP/N2/ABR was significantly lower than that in LoVo group（P〈0.05）. Conclusions： Target inhibiting the binding of cortex protein and Arp2/3 complex can inhibit the invasion and metastasis of colon cancer cell line, which may be achieved through the down-regulating of the expression of galectin-1.

关 键 词：肿瘤转移 结肠癌 皮层肌动蛋白 肌动蛋白 半乳糖凝集素 

分 类 号：R735.35[医药卫生—肿瘤]