经基因改造大肠杆菌DH5α对裸鼠结肠癌肝转移灶的治疗效果  

Gene modified Ecoli DH5α for the treatment of liver metastasis of colon cancer in nude mice

作　　者：姜宏华[1] 周辉[1] 张纪伟[1] 莱代莉[1] 子树明[1] 徐佶[1] 杜鹏[1] 杨宝仁[1] 崔龙[1] 

机构地区：[1]上海交通大学医学院附属新华医院肛肠外科,200092

出　　处：《实用医学杂志》2012年第13期2162-2165,共4页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:30950017)

摘　　要：目的:利用"与"门(AND gate)方法对缺氧敏感的甲酸脱氢酶基因操纵子、能感知细胞密度差异的lux基因转录启动子、白喉毒素基因等基因进行构建,导入NTG诱导的减毒营养缺陷型DH5α大肠杆菌(Ecoli DH5α),注射入荷瘤鼠,观察其对结肠癌肝转移灶的作用。方法:先构建质粒,然后导入诱变后DH5α大肠杆菌,注射入10只裸鼠体内,观察其毒性。后对20只结肠癌肝转移的荷瘤鼠注射后观察疗效。结果:注射野生型DH5α大肠杆菌10只裸鼠均死亡,而注射营养缺陷型DH5α大肠杆菌只有1只死亡,与未转染质粒的营养缺陷型DH5α大肠杆菌相比,注射含质粒的营养缺陷型DH5α大肠杆菌荷瘤鼠的癌转移灶大小明显小于对照组。结论:含"与"门质粒的营养缺陷型DH5α大肠杆菌安全,对结肠癌肝转移荷瘤鼠有明显趋向性及治疗作用,可为临床治疗做一新探讨。Objective The operon of formic dehydrogenase gene which was sensitive to hypoxia, the promoter of lux gene which could perceive the difference of cell density, and diphtheria toxin gene were constructed by synthetic AND gate methods. Then all these kinds of gene were imported into auxotrophy Eeoli DH5α mutagenized by N-Methyl-N＇-nitro-N-nitrosoguanidine （NTG）, which was eventually injected into nude mice with colon cancer. And the efficacy of this gene modified Ecoli DH5α on the liver metastasis of colon cancer was observed. Methods The plasmid was constructed and imported into auxotrophy Ecoli DH5α, and then the Ecoli DH5α was injected into 10 nude mice to observe the toxicity, and was injected into 20 nude mice with liver metastasis of colon cancer to observe the efficacy. Results Ten mice injected with wild type of Ecoli DH5α were all dead, and only one was dead of those injected with auxotrophy Eeoli DH5α. The size of liver metastasis of colon cancer in mice injected with auxotrophs Eeoli DH5α which contained plasmid was smaller than that contained no plasmid. Conclusion The auxotrophs Ecoli DH5α is safe for normal mice, and has chemotaxis and anti-tumor effect toward cancer foci.

关 键 词：结肠肿瘤 肝肿瘤 肿瘤转移 亚硝基胍 “与”门 DH5Α 大肠杆菌 

分 类 号：R735.35[医药卫生—肿瘤]