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化疗是治疗恶性肿瘤的主要方法之一,然而肿瘤细胞对化疗药物普遍产生的多重耐药性(multidrug resistance,MDR)是导致肿瘤治疗失败的主要原因.MDR的出现严重阻断了化疗药物的抗肿瘤效应,因此逆转MDR、提高化疗的成功率是肿瘤治疗中亟待解决的难题.在诸多因素引起MDR形式中,肿瘤细胞高水平表达MDR1 mRNA和P-gp最为常见.为了阻断MDR1 mRNA和P-gp的表达,逆转肿瘤细胞的多药耐药性,从理论上说至少可以在DNA、RNA和蛋白质3个环节入手,从蛋白质水平上逆转MDR可应用化学调节剂(如:Verapamail和Cyclosporin A),但它们缺乏特异性或毒副作用较大,因而在临床应用方面受到限制.在RNA水平上,应用抗MDR的核酶(ribozyme,Rz)技术是特异的、有效的策略之一.我们以往的研究表明抗MDR核酶的切割活性依赖于Rz和底物RNA的分子比.利用高效转基因的载体、高表达的启动子、改进Rz的分子结构等能提高肿瘤细胞内Rz的浓度和增加Rz结构的稳定性.因此在我们以往的工作基础上进
Chemotherapy is one of the main methods for the treatment of malignant tumors. However, the multidrug resistance (MDR) commonly caused by tumor cells is the main reason for the failure of tumor treatment. The emergence of MDR severely blocks the resistance of chemotherapy drugs. The tumor effect, therefore reversing MDR, increasing the success rate of chemotherapy is a difficult problem to be solved in the treatment of tumors. Among the MDR forms caused by many factors, high expression of MDR1 mRNA and P-gp are most common in tumor cells. In order to block MDR1 mRNA and P The expression of -gp reverses the multidrug resistance of tumor cells. Theoretically, it can be at least in DNA, RNA, and protein. Reversing MDR from the protein level can use chemical regulators (eg, Verapamail and Cyclosporin A). ), but they lack specificity or toxic side effects and are therefore limited in clinical applications. At the RNA level, the use of anti-MDR ribozyme (Rz) technology is one of the specific and effective strategies. The research shows that the cleavage activity of anti-MDR ribozyme depends on the molecular ratio of Rz and substrate RNA. The use of highly efficient transgene vectors, highly expressed promoters, improved molecular structure of Rz, etc. Tumor cells Rz Rz concentration and increase the stability of the structure. Thus the basis of our previous work progress