顺铂干预小鼠Lewis肺癌的MMP-9、TIMP-1表达及其相关性  

Effect of cisplatin on expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 and their correlations in Lewis lung cancer in mice

作　　者：李春杰[1] 孙建立[1] 姜维洁[1] 刘苓霜[1] 孙玺媛[1] 范国忠[1] 

机构地区：[1]上海中医药大学附属龙华医院肿瘤三科,上海200032

出　　处：《癌症》2009年第7期685-690,共6页Chinese Journal of Cancer

基　　金：上海市教育委员会科研项目(No.06CZ004)~~

摘　　要：背景与目的:肺癌转移是疾病进展和治疗失败的主要原因,基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、组织金属蛋白酶抑制物-1(tissue inhibitor of metalloproteinase-1,TIMP-1)作为调控细胞外基质降解的蛋白与肺癌转移关系密切。本研究观察顺铂对Lewis肺癌MMP-9和TIMP-1表达的影响,并探讨两者的关系和在转移中的作用。方法:建立Lewis肺癌C57BL/6小鼠肿瘤模型,顺铂组予以腹腔内注射顺铂溶液,以正常小鼠和荷瘤小鼠作对照。采用ELISA法和免疫组化法检测MMP-9、TIMP-1在血清和瘤体中的表达。结果:顺铂抑瘤率41.2%,抑制转移率39.0%。荷瘤小鼠瘤体中MMP-9、TIMP-1阳性率均为100%,血清浓度均高于正常对照组(P<0.05);顺铂组的血清MMP-9、TIMP-1浓度和瘤体MMP-9阳性率均低于荷瘤对照组(P<0.05)。血清及瘤体的MMP-9表达、瘤体TIMP-1表达均与瘤重、肺转移数成正相关(P<0.05)。血清及瘤体的MMP-9表达与TIMP-1表达均成正相关(r=0.617和0.695,P<0.05);血清MMP-9/TIMP-1的比值趋向于一个常量,其数值呈正态分布,均数为1.72。结论:Lewis肺癌中MMP-9和TIMP-1均呈高表达,两者与癌细胞的浸润和转移均有关;顺铂对血清MMP-9、TIMP-1浓度和瘤体MMP-9表达的下调作用是其抗转移作用的机理之一。Background and Objective： Metastasis of lung cancer is the leading cause of disease progression and treatment failure. Matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） are related to the metastasis of lung cancer via regulating the degradation of extracellular matrix. This study was to observe the impacts of cisplatin （DDP） on the expression of MMP-9 and TIMP-1 in Lewis lung cancer, and explore their correlations and roles in metastasis. Methods： Lewis lung cancer model was established in C57BL/6 mice. DDP group was given intraperitoneal DDP injection, and compared with normal control and tumor-bearing groups. The expression of MMP-9 and TIMP-1 were determined by ELISA in serum and detected by immunohistochemistry in tumor tissues. Results： The inhibition rates of tumor growth and metastasis were 41.2% and 39.0% in DDP group, respectively. The positive rates of MMP-9 and TIMP-1 were 100% in tumorbearing group, and their serum concentrations were significantly higher in tumor-bearing group than in normal control group （P〈0.05）. Serum concentrations of MMP-9 and TIMP-1, and positive rate of MMP-9 were all significantly lower in DDP group than in tumor-bearing group （P〈0.05）. Serum concentration of MMP-9 and positive rates of MMP-9 and TIMP-1 were positively correlated to tumor weight （r=0.665, 0.749 and 0.615, all P〈0.05） and lung metastasis （r=0.668, 0.545 and 0.664, all P〈0.05）. MMP-9 expression was positively correlated to TIMP-1 expression both in serum and tumor （r：0.617 and 0.695, all P〈0.05）. The ratio of sMMP-9/TIMP-1 became a constant in normal distribution, with a mean of 1.72. Conclusions： Both MMP-9 and TIMP-1 are highly expressed in Lewis lung cancer, correlated to tumor invasion and metastasis. DDP may suppress tumor metastasis via down-regulating the expression of MMP-9 and TIMP-1 in serum and tumor.

关 键 词：LEWIS肺癌 顺铂 转移 MMP-9 T1MP-1 小鼠 

分 类 号：R734.2[医药卫生—肿瘤]