肝癌耐药的基因学研究进展

Recent genomic research and development of hepatocarcinoma multidrug resistance

目的:总结肝癌耐药相关基因的研究进展。方法:应用Medline及CNKI期刊全文数据库检索系统,以"肝癌、耐药和基因"为关键词,主要检索2000-2011年肝癌耐药基因方面研究的相关文献129篇。纳入标准:1)肝癌耐药期;2)肝癌多药耐药;3)肝癌耐药机制;根据纳入标准共31篇文献纳入分析。结果:MDR,MRP,LRP,BCRP,GST,TOPO,Bcl-2,Survivin,p53,HIF-1,ErbB-2/neu,Rb,c-myc,Clusterin,PYK-2等基因及表达产物主要通过增加药物向细胞外转运,促进药物的代谢,促进细胞的增殖,抑制细胞的凋亡,诱导细胞的缺氧,上调原癌基因,参与细胞信号转导入等机制在肝癌耐药形成中起一定作用。其中MDR,MRP,LRP,BCRP作用机制已较清楚,其他基因与肝癌耐药有明显相关性。结论:筛选并深入研究肝癌耐药相关基因,从基因水平探索肝癌耐药机制,有望为逆转肝癌耐药提供新的途径。

OBJECTIVE： To summary the recent researches of hepatocarcinoma multidrug resistance-related genes. METHODS：Literature about hepatocarcinoma multidrug resistance-related Genes were searched for with hepatoearcinoma, multidrug resistance and gene as keywords in Medline and CNKI date-base mainly from 2000 to 2011. And 129 literatures were got Inclusion criteria：resistance genes; multidrug resitance; mechanism of resistance. According to the criteria,31 papers were analyzed. RESULTS： MDR, MRP, LRP, BCRP, GST, TOPO, Bcl-2, Survivin, p53, HIF-1, ErbB-2/neu, Rb, c myc,Clusterin,PYK-2 genes and relevant expressed products play a role in the formation of hepatocarcinoma multidrug resistance,mainly through accelerating drug transfer to the extraeellular, promoting drug metabolism, promoting cell pro- liferation, inhibiting apoptosis, inducing hypoxia, upregulating oncogene and involving in cell signal transduction. The mechanism of MDR, MRP,LRP,BCRP has been more clear,others associated with the resistance of multidrug resistance of hepatocarcinoma significantly. CONCLUSION： Screening and in-depth studyding of hepatocarcinoma multidrug resist- ance-related genes, exploring the mechanism from gene level, are expected to provide new ways of reversing hepatocarcino- ma multidrug resistance.