罗格列酮联用维甲酸在体内对直肠癌HCT-15细胞COX-2、MMP-7、TIMP-1表达的影响  

In vivo effect of rosiglitazone combined with all-trans retinoic acid on the expression of COX-2、MMP-7、TIMP-1 0f rectal cancer HCT-15 cells

作　　者：王猛[1] 苗瑞政[1] 徐涛[1] 郭仁乐[1] 姜言明[1] 

机构地区：[1]山东大学附属省立医院胃肠外科,山东济南250021

出　　处：《中国现代普通外科进展》2011年第7期505-508,共4页Chinese Journal of Current Advances in General Surgery

摘　　要：目的:研究罗格列酮(ROS)联用全反式维甲酸(ATRA)对直肠癌裸鼠移植瘤HCT-15细胞COX-2、MMP-7、TIMP-1表达的影响,并初步探讨其抗肿瘤的机制。方法:建立直肠癌裸鼠移植瘤模型,荷瘤裸鼠随机分为未用药组、ROS组(ROS 25 mg.kg-1.2d-1)、ATRA组(ATRA 11mg.kg-1.2d-1)、ATRA联用ROS组[(ROS 25 mg+ATRA 11 mg).kg-1.2d-1]。灌胃40 d后,观察各组裸鼠移植瘤体积变化;利用免疫组化SP法观察移植瘤细胞中COX-2、MMP-7、TIMP-1的表达。结果:1)用药3组瘤体体积与未用药组比较均缩小,差别有统计学意义(P<0.05),ATRA联用ROS组的荷瘤体积缩小更明显(P<0.05);ROS组与ATRA组瘤体体积相当(P>0.05);2)用药3组移植瘤细胞内COX-2、MMP-7、TIMP-1的表达与未用药组比较均降低(P<0.05),且ROS组与ATRA组移植瘤细胞内COX-2、MMP-7、TIMP-1下降更明显(P<0.01),ROS组与ATRA组移植瘤细胞内三者的表达相当(P>0.05)。结论:ROS与ATRA均有一定的抑瘤作用,ROS与ATRA联用可发挥协同抗肿瘤的作用,可能是通过抑制移植瘤细胞内COX-2、MMP-7、TIMP-1的表达而实现。Objective： To investigate the effect of rosiglitazone（ROS） combined with all-trans retinoic acid（ATRA） on the expression of COX-2、MMP-7、TIMP-1 of transplanted rectal cancer in nude mice,and to explore the mechanism of anti-carcinoma preliminarily.Methods： Established the modle of transplanted tumor in node mice by inoculating human rectal cancer cell line HCT-15 into the right back of nude mice subcutaneously.The cancer-bearing nude mice were divided randomly into 4 groups： group 1 with no drugs,group 2 with ROS（ROS 25 mg）·kg-1·2d-1,group 3 with ATRA（ATRA 11 mg·kg-1·2d-1）,group 4 ROS combined with ATRA [（ROS 25 mg＋ ATRA 11mg）·kg-1·2d-1].After treated for 40 days,the volume change of tumor were observed.The expression of COX-2、MMP-7、TIMP-1 in transplanted tumor cells were detected by immunohistochemical.Results： 1）The volumes of tumor were significantly decreased in group 2、3、4 compared with group 1（P0.05）,The volume of tumor in group 4 was significantly decreased compared with group 2、3（P0.05）,The volume of tumor in group 2 was similar to group3（P0.05）.2）The expression of COX-2、MMP-7、TIMP-1 in transplanted tumor were significantly decreased in group 2、3、4 compared with group 1（P0.05）,The expression of COX-2、MMP-7、TIMP-1 in group 4 were significantly decreased compared with group 2、3（P0.01）.The expression of these three in group2 and group3 were quite（P0.05）.Conclusion： ROS and ATRA can inhibit the growth of tumor and ROS combined with ATRA can further inhibit the growth of tumor.The mechanism maybe that ROS and ATRA can inhibit expression of COX-2、MMP-7、TIMP-1.

关 键 词：罗格列酮 维甲酸 环氧化酶-2 基质金属蛋白酶 组织型基质金属蛋白酶抑制物 

分 类 号：R735.37[医药卫生—肿瘤]