造血干细胞多药耐药P-糖蛋白的表达及多药耐药逆转剂对其功能的影响

The Expression of P-glycoprotein in Hemapoietic Stem Cells and the Influence of Multidrug Resistance Modifier to the Activity of P-glycoprotein

目的 :了解多药耐药 P-糖蛋白 ( P- gp)在造血干 /祖细胞的表达 ,探讨多药耐药逆转剂在临床应用过程中可能对造血干细胞的损害。方法 :采用 MRK16单克隆抗体 ,利用流式细胞仪测定健康人骨髓 CD34 阳性细胞表面 P- gp的表达 ;将多药耐药逆转剂 MS- 2 0 9作用于造血细胞 ,检测 MS- 2 0 9对 CD34 阳性细胞摄取染料 Rhodamin- 12 3的影响。结果 :骨髓 CD34 阳性细胞的 P- gp表达率为13.3% ,MS- 2 0 9明显增加 CD34 阳性细胞对 Rhodamin- 12 3的摄入 ( 18.1% )。结论 :造血干细胞表达P- gp蛋白并且具有活性功能 ;多药耐药逆转剂可以抑制其 P- gp的膜泵出功能 ,提示在临床应用中可能会增加化疗药物对造血干细胞的损害。

Objective:To investigate the possible clinical side effect of multidrug resistance (MDR) modifier to hemapoietic stem cells during chemotherapy.Method:The expression and activity of MDR P-glycoprotein (P-gp) in CD 34 positive subpopulation from normal bone marrow cells were detected using MRK16 monoclonal antibody and a new MDR modifier MS-209 with flowcytometry techn.Result:The expression of P-gp in the CD 34 positive subpopulation in normal bone marrow were confirmed (positive rate were 13.3 %),MS-209 can significantly increase the uptake of Rhodamin-123 of CD 34 positive cells (increase rate were 18.1 %).Conclusion:MDR modifier can inhibit the function of P-gp CD 34 positive cells.The clinical using of MDR modifier possibly increase the cytotoxicity of antitumor drugs to normal hemapoietic stem cells.