红霉素对人类白血病细胞系CCRF-CEM/VLB100耐药性逆转作用的研究

本文报告,亲脂性抗生素红霉素在体外培养条件下,成功地逆转了人类淋巴细胞白血病细胞系CCRF-CEM/VLB100对长春花碱的耐药性。免疫荧光检测证实,耐药细胞膜上有P-糖蛋白高表达,阳性率为94％;敏感细胞则无P-糖蛋白表达。耐药细胞经红霉素作用后,P-糖蛋白阳性半降至30％以下。据此认为,红霉素使耐药细胞膜上P-糖蛋白表达降低,阻断了耐药细胞泵出药物的功能,可能是其逆转耐药性的基础。我们首次将红霉素用于人类白血病细胞系,对耐药性逆转作用的实验研究及临床应用均有积极的意义。

REVERSAL OF CEM/VLB100 CELL RESISTANCE TO VINBLASTINE BY ERYTHROMYCIN IN VITRO

The lipophilic antibiotic, erythromycin, proved to be able to reverse the resistance of CEM/VLB100 cells to vinblastine in this study. The MDR cells showed a 94% over-expression of P-glycoprotein, while the drug-sensitive parent line showed no expression of P-glycoprotein, as revealed by immunofluorescent assay. Erythromycin can reduce the P-glycoprotein expression rate of the resistant cells to less than 30%. This result suggests that erythromycin can reverse drug resistance by saturating the drug-binding sites on the P-glycoprotein, thereby reducing the capacity Of this protein to pump drugs out of resistant cells. We attempt to administer erythromycin as a revertant agent against human leukemic cells has thrown a new light on the clinical management of leukemia.