基因重组心肌肌钙蛋白Ⅰ融合蛋白的抗肿瘤效应  

Inhibitory effect of tumor growth of recombinant protein fused with cardiac troponin Ⅰ and artificial peptide

作　　者：雷光强[1] 刘朝阳[2] 姜懿纳 李金萍[4] 曹勤燕[1] 李涛[5] 刘凤鸣[1] 

机构地区：[1]广西药用植物研究所,广西南宁530024 [2]中国医学科学院肿瘤研究所,北京100021 [3]湖南中医药大学药学院,湖南长沙410208 [4]常州大学制药与生命科学学院,江苏常州213016 [5]中国医学科学院基础医学研究所,北京100050

出　　处：《中国药理学通报》2015年第11期1580-1585,共6页Chinese Pharmacological Bulletin

基　　金：广西科学研究与技术开发计划(No桂科攻14124004-2-14)

摘　　要：目的研究基因重组心肌肌钙蛋白I与人工短肽的融合蛋白(CIS)对肿瘤生长的作用。方法用MTT法观察CIS体外对人脐静脉内皮细胞(HUVEC)生长的作用。利用鸡胚绒毛尿囊膜模型观察CIS对新生血管生长的影响。用6种小鼠肿瘤异位可移植模型观察CIS在体内对肿瘤生长的作用。结果 CIS对HUVEC细胞增殖具有明显抑制作用,并呈剂量依赖关系;鸡胚绒毛尿囊膜实验显示,CIS浓度为5、10 mg·L^(-1)时,新生血管生成的数量明显减少;荷瘤鼠体内异位移植模型实验显示:CIS(10 mg·kg^(-1))处理组肿瘤生长缓慢,瘤体明显小于模型对照组,对S180肿瘤瘤重抑制率85.3%,对Lewis肺癌肿瘤瘤重抑制率87.0%,对H22肝癌肿瘤瘤重抑制率84.2%,对人小细胞肺癌H446肿瘤瘤重抑制率60.42%,对人可移植性肝癌SMMC7721肿瘤瘤重抑制率61.62%,对人胃低分化腺癌BGC823肿瘤瘤重抑制率为41.84%。结论 CIS在体外抑制HUVEC细胞的生长,在鸡胚绒毛尿囊膜实验中,CIS对新生血管生成有明显的抑制作用。在体内,CIS融合蛋白可有效抑制小鼠可移植肿瘤细胞的生长。CIS抗肿瘤效应很可能是通过抑制肿瘤组织中血管内皮细胞的增殖,进而减少肿瘤组织中新生血管生成的数量而达到的。Aim To examine the inhibitory effect of re-combinant cardiac troponin fusion protein composed of subunit I and artificial peptide which was called CIS on tumor growth. Methods The CIS ’ s effect on the growth of human umbilical vein endothelial cells ( HU-VEC) was examined using MTT assay in vitro. Chick chorioallantoic membrane model was applied to study the alteration of angiogenesis treated with purified re-combinant CIS protein. The effect of tumor growth trea-ted with CIS was observed using several in vivo mice xenograft models. Results There was a statistically significant reduction in HUVEC cell proliferative rate when the cells were treated with purified CIS fusion protein, which was also shown in a dose-dependent manner. A decreased amount of new blood vessel for-mation ( angiogenesis) on chick embryo chorioallantoic membranes was observed in recombinant CIS protein treated group compared to the untreated control group. A significant inhibition of tumor growth rate was a-chieved in CIS treated mice compared to CIS untreated control mice in 6 different mouse xenograft models. Conclusions The fusion protein CIS shows the inhibi-tory effect on the tumor growth in our in vivo mouse models, and such inhibition could be mediated by the mechanism of CIS’ s effect on the decrease of HUVEC cell proliferation and further the reduction of angiogen-esis in tumor tissues. This work could provide the foundation for the in-depth investigations on the phar-maceutical application of CIS targeting anti-tumor ther-apy.

关 键 词：基因重组心肌肌钙蛋白融合蛋白 人脐静脉内皮细胞 鸡胚绒毛尿囊膜 移植瘤 肿瘤抑制作用 血管生成抑制剂 裸鼠 

分 类 号：R-332[医药卫生] R322.12