K562／H20和K562／Mel细胞株对高三尖杉酯碱与马法兰耐药机制的比较研究

Acomparativestudyonmechanismsofhomoharringtonine(HHT)andmelphalan(Mel)resistanceinK562/H20andK562/Melcelslines

为比较高三尖杉酯碱和马法兰的耐药机制，对天然来源抗肿瘤药物高三尖杉酯碱耐药株Ｋ５６２／Ｈ２０与烷化剂马法兰耐药株Ｋ５６２／Ｍｅｌ耐药机制进行研究，发现前者对长春新碱、柔红霉素、阿霉素具有广泛交叉耐药，对马法兰耐药水平较低；后者对氮芥、噻替派有明显交叉耐药。在耐药机制上，前者主要由于多药耐药基因过度表达所致，谷胱甘肽－Ｓ－转移酶（ＧＳＴ）π、α基因也参与部分耐药机制；后者主要由于ＧＳＴα基因及ＧＳＴ总活性所致。两者似乎均通过ＧＳＴα基因表达升高起作用。

Tostudythedrugresistancemechanismofhomoharringtonine(HHT)andmelphalan(Mel),drugresistancemechanismsbetweentwoK562sublines:onebeingHHT-resistant(K562/H20)andtheother,melphalanMel-resistant(K562/Mel),werecompared.TheresultsshowedthatK562/H20wasresistanttoHHT,vincristine(VCR),doxorubicin(DOX),daunorubicin(DNR)andMel,whileK562/MelresistanttoMel,Nitrogenmustardsandthiophosphoramide,butnottoDOXandVCR.ResistancetoHHTinvolvedinenhancingcelulardrugefluxasaresultofMDR-1geneoverexpressionandpartlyintheincreasingexpressionlevelofGSTπandαgenes.ResistancetoMelinvolvedinthein-creaseofexpressionofGSTαgeneandtotalGST,butnotinincreaseofexpresionofGSTπ,μ,MDR-1andTopoⅡ.