基因重组心肌肌钙蛋白Ⅰ融合蛋白的抗肿瘤效应

发布时间：2018-04-22 08:50

本文选题：基因重组心肌肌钙蛋白融合蛋白 + 人脐静脉内皮细胞　；参考：《中国药理学通报》2015年11期

【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。
[Abstract]:Objective to study the effect of recombinant cardiac troponin I and artificial short peptide fusion protein CISS on tumor growth. Methods the effects of CIS on the growth of human umbilical vein endothelial cells (HUVECs) were observed by MTT method in vitro. The effect of CIS on neovascularization was observed by chorioallantoic membrane model of chicken embryo. The effects of CIS on tumor growth in vivo were observed in 6 heterotopic mouse models. Results CIS significantly inhibited the proliferation of HUVEC cells in a dose-dependent manner, and the chorioallantoic membrane assay showed that the number of neovascularization was significantly decreased at the concentration of 5 ~ 10 mg / L ~ (-1) in chorioallantoic chorioallantoic chorioallantoic cells. The experimental results of heterotopic transplantation showed that the tumor growth was slower and the tumor body in the treated group was significantly smaller than that in the model control group. 85.3% of S180 tumor, 87.0% of Lewis lung cancer, 84.2% of H22 liver cancer, 60.42% of human small cell lung cancer H446, 61.62% of human transplantable liver cancer SMMC7721 tumor, 61.62% of human stomach cancer, 84.2% of H22 tumor weight inhibition rate, 85.3% of S180 tumor weight inhibition rate, 87.0% of Lewis lung cancer tumor weight inhibition rate, 84.2% of H22 tumor weight inhibition rate, 60.42% of human small cell lung cancer H446 tumor weight inhibition rate. The weight inhibition rate of BGC823 tumor in low differentiated adenocarcinoma was 41. 84%. Conclusion CIS can inhibit the growth of HUVEC cells in vitro and inhibit angiogenesis in chorioallantoic membrane test. In vivo, CIS fusion protein can effectively inhibit the growth of transplanted mouse tumor cells. The anti-tumor effect of CIS may be achieved by inhibiting the proliferation of vascular endothelial cells in tumor tissues and thus reducing the number of angiogenesis in tumor tissues.
【作者单位】：广西药用植物研究所;中国医学科学院肿瘤研究所;湖南中医药大学药学院;常州大学制药与生命科学学院;中国医学科学院基础医学研究所;
【基金】：广西科学研究与技术开发计划(No桂科攻14124004-2-14)
【分类号】：R965

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