论文部分内容阅读
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 study the mechanism and reversal of multidrug resistance (MDR) in human leukemia cells. Methods Two MDR cell lines, K562 / HHT and K562 / VCR, were established. Expressions of Pgp and MDR-related proteins (MRP) were observed by immunohistochemical staining. Drug susceptibility testing and determination of intracellular daunorubicin (DNR) content of verapamil and erythromycin MDR reversal effect. Results Both MDR cell lines showed high expression of Pgp but no MRP expression. Both 5μg / ml verapamil and 50μg / ml erythromycin partially reversed the drug resistance of the two MDR cell lines. 2.5 ~ 10μg / ml verapamil can not only increase the uptake of DNR in MDR cells, but also reduce the efflux of DNR, and the above effect increases with the increase of verapamil concentration; 50 ~ 200μg / ml erythromycin MDR cell uptake and efflux DNR no significant effect. Conclusion Pgp may be related to the production of MDR in leukemia cells. Verapamil and erythromycin may reverse MDR in leukemia cells.