MMP-2和ICAM-1在裸鼠体内塞来昔布抑制肝癌组织中的表达  

Celecoxib inhibits the expression of MMP-2 and ICAM-1 in hepatocellular carcinoma xenografts in nude mice

作　　者：殷积彬[1] 李宝馨[2] 谢新玉[3] 刘冰熔[1] 吕志武[1] 关景明[1] 高善玲[1] 

机构地区：[1]哈尔滨医科大学附属第二医院消化科,黑龙江省哈尔滨市150081 [2]哈尔滨医科大学药学院药理学教研室,黑龙江省哈尔滨市150081 [3]北京市朝阳区垂杨柳医院消化一科,北京市100025

出　　处：《世界华人消化杂志》2010年第12期1206-1210,共5页World Chinese Journal of Digestology

基　　金：黑龙江省教育厅科学技术研究基金资助项目;No.11521184~~

摘　　要：目的:研究机体内部选择性环氧合酶-2(COX-2)抑制剂对肝细胞癌的抑制作用.方法:将三种肝癌细胞株HepG2、BEL-7402和SMMC-7721分别接种于6周龄裸鼠肝脏被膜下;将接种了不同肝癌细胞株的裸鼠分别分为3组,阴性对照组给予生理盐水灌胃,实验组给予塞来昔布灌胃,阳性对照组进行生理盐水灌胃的同时使用阿霉素腹腔注射;3wk后对裸鼠肝脏肿瘤取材、免疫组织化学法观察肿瘤组织中基质金属蛋白酶-2(MMP-2)及其抑制剂(TIMP-2)以及细胞间黏附因子-1(ICAM-1)的表达.结果:在肝脏被膜下接种了HepG2、BEL-7402和SMMC-7721肝癌细胞株的裸鼠中,应用塞来昔布的裸鼠肿瘤组织中MMP-2的表达下降(P<0.05),MMP-2的表达增加(P<0.05),TIMP-2/MMP-2比值增加.在肝脏被膜下接种了BEL-7402和SMMC-7721肝癌细胞株的裸鼠中,应用塞来昔布的裸鼠肿瘤组织中ICAM-1表达下降.结论:塞来昔布在机体内部可能具有抑制肝癌细胞转移和改善预后的作用.AIM：To investigate the antitumor effects of celecoxib （a selective cyclooxygenase-2 inhibitor） against hepatocellular carcinoma in vivo.METHODS：Human hepatoma cells （HepG2,BEL-7402 and SMMC-7721） were injected beneath the hepatic capsule of six-week-old nude mice.The mice were then randomly divided into three groups：negative control group （intra-gastrically given normal saline）,experimental group （intragastrically given celecoxib）,and positive control group （intragastrically given normal saline and intraperitoneally injected with adriamycin）.Three weeks later,tumor tissue samples were taken for immunohistochemical analysis to examine the expression of matrix metalloproteinase-2 （MMP-2）,tissue inhibitor of metalloproteinases-2 （TIMP-2） and intercellular adhesion molecule-1 （ICAM-1）.RESULTS：Compared to the negative control group,the expression of MMP-2 was downregulated （P 0.05） and that of TIMP-2 was upregulated （P 0.05） in hepatocellular carcinoma xenografts derived from HepG2,BEL-7402 and SMMC-7721 cells in the experimental group.The expression ofiCAM-1 was also down-regulated in hepatocellular carcinoma xenografts derived from BEL-7402 and SMMC-7721 cells in the experimental group when compared with the negative control group （P 0.05）.CONCLUSION：Celecoxib may be able to inhibit the metastasis and improve the prognosis of hepatocellular carcinoma.

关 键 词：选择性环氧合酶-2抑制剂 肝癌 基质金属蛋白酶-2 细胞间黏附因子-1 

分 类 号：R735.7[医药卫生—肿瘤]