RNA干扰在逆转白血病细胞多药耐药方面的应用

RNA Interference Used for Reversal of Multi-drug Resistance in Leukemia Cells—— Review

化疗一直作为临床上治疗白血病(leukemia)的首选方法。然而,白血病细胞对化疗药物产生的多药耐药严重影响了化疗效果,是导致治疗失败和疾病复发的主要原因。因此,探索出一条安全有效的逆转耐药途径已成为白血病治疗成功与否的关键。RNAi(RNA interference)即RNA干扰,是生物界中一种古老且进化上高度保守的基因沉默现象,它是指在双链RNA(double-stranded RNA,dsRNA)的介导下,特异性降解对应序列的mRNA,从而抑制相应基因表达的一种基因阻断过程,可诱发转录后水平上的基因沉默(post-transcriptional genes ilencing,PTGS)。RNAi最大的优点在于其特异性和高效性,可高度特异地使与之同源的mRNA降解,而无关基因不受影响。现在,作为一种研究工具,该技术已广泛应用于生物医药的各个领域,特别是在血液系统肿瘤的诊断和治疗中的作用越来越突出。然而,这种新兴的基因功能研究技术,因其在体内的稳定性、作用的靶向性和遗传学上的生物安全性等方面的限制,在临床应用中遇到了发展的瓶颈。此外,外源RNA应用于人体所引起的免疫反应也是制约RNAi技术应用于临床的关键因素。本文以RNA干扰技术作为切入点,综述了该技术在白血病多药耐药逆转研究方面的进展。

Chemotherapy remains at the first line for the treatment of leukemia. However, the multi-drug resistance of the tumor cells caused by chemotherapeutic drugs has seriously affected the effect of chemotherapy. And this is the main reason for the failure of the leukemia treatment. Therefore, to explore an effective way of reversing drug resistance has become the key of leukemia treatment. RNA interference, a system within living cells, helps to determine which genes are active and how active they are. It is a process in which translation of some cell messenger RNA （mRNA） sequences is prevented, because of the presence of （and consequent destruction of） matching double-stranded RNA sequences. RNA interference is also called post-transcriptional gene silencing （PTGS）, since its effect on gene expression occurs after the production of mRNA during transcription. It is believed that RNA interference can protect the cell against viruses and other threats. The greatest advantage of RNAi is the specificity and high efficiency which can induce suppression of specific genes of interest but the unrelated genes are not affected. The selective and robust effect of RNAi on gene expression makes it a valuable research tool both in cell culture and living organisms because synthetic dsRNA introduced into cells can induce the suppression of specific genes of interest. Nowadays, the technology has been widely used in biomedical fields, especially in the diagnosis and treatment of blood system disease. However, besides the stability, targeting and biological safety in genetics, the immune response induced by exogenous RNA is also one of the key factors to limit the clinical practice of this emerging technology. In this review, the breakthrough of the technology in multi-drug resistance reversal in leukemia is summarized with the RNA interference technology as a starting point.