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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: To construct hypoxia-inducible formate dehydrogenase gene operon, lux gene transcriptional promoter and diphtheria toxin gene which are sensitive to cell densities using the AND gate method. Of attenuated auxotrophic DH5α Escherichia coli (Ecoli DH5α), injected into tumor-bearing mice to observe its role in liver metastases of colon cancer. Methods: The plasmids were constructed first, and then induced into E. coli DH5α after mutagenesis, injected into 10 nude mice to observe their toxicity. Twenty tumor-bearing mice with liver metastasis of colon cancer were observed after injection. Results: 10 wild-type DH5α-infected E. coli were killed, while only 1 death was induced by injection of auxotrophic DH5α E.coli. Compared with untransfected plasmids, auxotrophic DH5α- The size of cancer metastasis in DH5α-bearing mice was significantly smaller than that in control group. Conclusion: The safety of auxotrophic DH5α Escherichia coli harboring the “” and “” plasmids is safe and has obvious tendency and therapeutic effect on liver metastasis of colon cancer and can be a new exploration for clinical treatment.