异搏定对白血病K562细胞耐药性的逆转作用

Reversing Effect of Verapamil on Multidrug Resistance in Human Leukemia K562 Cells

目的 :研究异搏定对 P-糖蛋白 (Pgp)介导的人类白血病 K 5 6 2细胞多药耐药作用。方法 :用台盼蓝拒染法检测药物敏感性及异搏定对细胞耐药性的影响 ,用免疫组织化学法检测 Pgp的表达 ,用流式细胞仪检测细胞内柔红霉素 (DNR)积聚。结果 :DNR诱导的耐药细胞 K5 6 2 / D对 DNR、长春新碱 (VCR)、高三尖杉脂碱 (HHT)、鬼臼乙叉甙 (VP16 )、米托恩醌 (MIT)交叉耐药。 DNR诱导了 K5 6 2 / D细胞的 Pgp过度表达。异搏定使 K 5 6 2 / D细胞内药物积聚增加 ,明显地逆转了 K5 6 2 / D细胞对 DNR、VCR、MIT、HHT、VP- 16的耐药性 ,而对敏感细胞 K5 6 2 / S的耐药性无影响。结论 :DNR诱导了 K5 6 2 / D细胞的 Pgp过度表达 ,异搏定通过抑制 Pgp功能逆转了 Pgp介导的K5 6 2 /

Objective: This test was designed to study the effects of verapamil on P glycoprotein (Pgp) mediated multidrug resistance (MDR) in human leukemia K562 cells. Methods: Trypanblue dye exclusion method was used to observe the drug sensitivity and the effect of verapamil on the drug resistance; immunohistochemical technique to analyze Pgp phenotype, and flow cytometer was used to measure the intracellular drug accumulation. Results: Resistant cells (K562/D) induced by DNR were cross resistant to DNR, HHT, VP16 and MIT. DNR induced overexpression of Pgp in K562/D cells; Verapamil increased the intracellular drug accumulation, and then obviously reversed the drug resistance to DNR, VCR, MIT, HHT, and VP 16 in K562/D cells, but not in the sensitive cells (K562/S). Conclusion: The multidrug resistance of K562/D cells can be induced by DNR which is related to the Pgp overexpression, and verapamil reversed the DNR resistance by increasing the intracellular accumulation of DNR.