多药耐药细胞系K562/HHT和K562/VCR的建立及耐药性逆转的研究  

Establishment of multidrug resistant cell lines K562/HHT and K562/VCR and reversal of drug resistance

作　　者：石淑文[1] 郭淑芬[1] 

机构地区：[1]浙江医科大学附属儿童医院

出　　处：《中华儿科杂志》1998年第1期15-18,共4页Chinese Journal of Pediatrics

摘　　要：目的研究人白血病细胞多药耐药（ＭＤＲ）的发生机理及逆转方法。方法建立了Ｋ５６２／ＨＨＴ和Ｋ５６２／ＶＣＲ两株ＭＤＲ细胞系，经免疫组化染色观察了Ｐ－糖蛋白（Ｐｇｐ）和ＭＤＲ相关蛋白（ＭＲＰ）的表达；采用四氮甲基唑蓝（ＭＴＴ）药敏试验及测定细胞内柔红霉素（ＤＮＲ）含量的方法研究了异搏定和红霉素对ＭＤＲ的逆转作用。结果两株ＭＤＲ细胞系均有Ｐｇｐ高度表达，但无ＭＲＰ表达。５μｇ／ｍｌ异搏定和５０μｇ／ｍｌ红霉素都能部分逆转两株ＭＤＲ细胞系的耐药性。２．５～１０μｇ／ｍｌ异搏定不仅能增加ＭＤＲ细胞对ＤＮＲ的摄取量，也能减少ＤＮＲ的外排，且上述作用随异搏定浓度的增加而增强；５０～２００μｇ／ｍｌ红霉素则对ＭＤＲ细胞摄取和外排ＤＮＲ无明显影响。结论Ｐｇｐ可能与白血病细胞产生ＭＤＲ有关；异搏定和红霉素对白血病细胞ＭＤＲ有逆转作用。Objective To investigate the mechanism of multidrug resistance (MDR) in human leukemic cells and the way to overcome MDR. Methods The authors established two MDR cell lines K562/HHT and K562/VCR. The expressions of P glycoprotein (Pgp) and MDR related protein (MRP) in the two MDR cell lines were observed by immunohistochemical staining and the reversal of MDR by verapamil and erythromycin was studied by MTT assay or by the determination of the amount of daunorubicin (DNR) in cells. Results The two MDR cell lines overexpressed Pgp but didn′t express MRP. The drug resistance of the two MDR cell lines could be partly reversed by 5 μg/ml of verapamil or 50 μg/ml of erythromycin. 2.5～10 μg/ml of verapamil increased DNR accumulation and retention in the two MDR cell lines, and the effect became obvious along with an increase in verapamil concentration. 50～200 μg/ml of erythromycin, however, did not impact DNR accumulation and retention in the two MDR cell lines. Conclusion Pgp might be in association with the MDR of leukemic cells. Verapamil and erythromycin could reverse the MDR of leukemic cells.

关 键 词：白血病 抗药性 多药 维拉帕米 红霉素 药物疗法 

分 类 号：R733.705[医药卫生—肿瘤]