多药耐药相关ABC转运蛋白信号转导通路研究进展

Multidrug resistance-associated ABC transporter signal transduction pathways:research progress

ATP结合盒(ABC)转运蛋白表达和功能的异常是造成多药耐药(MDR)的重要原因之一,其中P-糖蛋白、乳腺癌耐药蛋白和MDR相关蛋白在MDR发生中起着重要作用,是ABC转运蛋白家族中研究热点。本文对近几年来这3种转运蛋白相关信号转导通路进行整理分析,如NF-κB信号通路、丝裂原活化蛋白激酶级联信号通路、磷脂酰肌醇3-激酶/蛋白激酶B信号通路和音猬因子(sonic hedgehog)信号通路等,挖掘出信号通路中重要调控节点NF-κB、激活蛋白1、c-Jun和转录因子Gli等,具有成为MDR逆转剂作用靶点的可能性,以期为MDR机制研究及其逆转剂研发提供较系统的参考。

Disfunction of ATP-binding cassette(ABC) transporters will result in multidrug resistance(MDR). P-glycoprotein(P-gp), breast cancer resistance protein(BCRP) and multidrug resistanceassociated protein(MRP) play an important role in MDR. This review focused on signal pathways associated with P-gp, BCRP and MRP in recent years, such as nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB) signal transduction pathway, mitogen-activated protein kinase(MAPK) transduction pathway, phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) signal transduction pathway, and sonic hedgehog(Shh) signal transduction pathway. Important regulatory nodes NF-κB, activator protein 1(AP-1), c-Jun and Gli were analyzed, which have the potential to become a target for multidrug resistance reversal agents. This paper is intended to provide a systematic and forward-looking overview for study of multidrug resistance mechanisms and development of reversal agents.