CAJ | 학술논문

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。
목적：연구기인중조심기기개단백I 여인공단태적융합단백( CIS)대종류생장적작용。방법용MTT법관찰CIS체외대인제정맥내피세포( HUVEC)생장적작용。이용계배융모뇨낭막모형관찰CIS대신생혈관생장적영향。용6충소서종류이위가이식모형관찰CIS재체내대종류생장적작용。결과 CIS대HUVEC세포증식구유명현억제작용,병정제량의뢰관계；계배융모뇨낭막실험현시,CIS 농도위5、10 mg·L-1시,신생혈관생성적수량명현감소；하류서체내이위이식모형실험현시：CIS(10 mg·kg-1)처리조종류생장완만,류체명현소우모형대조조,대 S180종류류중억제솔85．3%,대Lewis폐암종류류중억제솔87．0%,대H22간암종류류중억제솔84．2%,대인소세포폐암H446종류류중억제솔60．42%,대인가이식성간암SMMC7721종류류중억제솔61．62%,대인위저분화선암BGC823종류류중억제솔위41．84%。결론 CIS재체외억제HUVEC세포적생장,재계배융모뇨낭막실험중,CIS대신생혈관생성유명현적억제작용。재체내,CIS융합단백가유효억제소서가이식종류세포적생장。 CIS항종류효응흔가능시통과억제종류조직중혈관내피세포적증식,진이감소종류조직중신생혈관생성적수량이체도적。
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.