骨肉瘤化疗多药耐药的分子机制及其逆转

目的：总结国内外对骨肉瘤化疗多药耐药的分子机制及相应逆转措施的研究进展;方法：应用PubMed及CNKI期刊全文数据库检索系统,以＂骨肉瘤、化疗多药耐药、机制、逆转＂等为关键词,检索2000-2011年的相关文献。纳入标准：1）骨肉瘤耐药相关的蛋白质、酶类及相关基因;2）各因素发挥作用的机制;3）相关的逆转措施。结果：骨肉瘤多药耐药是当今骨肉瘤化疗治疗的一大难题,多药耐药性即肿瘤细胞对一种抗肿瘤药物产生耐药性的同时,对其他结构和作用机制不同的多种药物产生交叉耐药性。其作用的发生是多种因素共同作用的结果。结论：与骨肉瘤化疗多药耐药相关的主要有P-糖蛋白,多药耐药相关蛋白,肺耐药蛋白,谷胱甘肽,拓扑异构酶,蛋白激酶C以及DNA损伤修复和细胞凋亡抑制等相关机制。而逆转措施主要通过抑制剂和基因疗法。

The Molecular Mechanism of Multidrug Resistance in Osteosarcoma and Reversal

Objective： Summary the progress of molecular mechanism of multidrug resistance in osteosarcoma and corresponding reversal measures at home and abroad. Methods： Retrieve the literature from 2000 to 2011 by applying retrieval system of the Pubmed and CNKI database. The criteria is： 1）The proteins, enzymes and related genes of drug-resistance in osteosarcoma. 2） The mechanism of various factors. 3） Reversal measures. Result： Multidrug-resistance is a major obstacle to the tumor chemotherapy currently. Tumor cells in vitro that have been exposed to singal antitumor drug can develop cross-resistance to the various drugs of different structure and mechanism, this phenomenon is called multi-drug resistance. Conclusion： The factors associated multidrug resistance of osteosarcoma were p-gp, MRP, LRP, GSH, TOPO Ⅱ, PKC, DNA damage repair mechanism and apoptosis suppression mechanism. The major reversal measures were inhibitors and gene therapy.