麻黄碱逆转K562/A02细胞多药耐药性的研究

Reversal of multidrug-resistance in K562/A02 cell by ephedrine

目的:观察非细胞毒性质量浓度的麻黄碱对耐药的白血病细胞株(K562/A02)多药耐药性的逆转作用,并探讨其逆转机制。方法:用MTT法检测麻黄碱的细胞毒作用;用流式细胞仪检测非细胞毒性浓度的麻黄碱处理后K562/A02细胞膜表面糖蛋白P170表达及功能的变化。结果:麻黄碱对K562/A02有一定的细胞毒作用,其非细胞质量浓度(IC10)为75mg.L-1,非细胞毒性质量浓度的麻黄碱对K562/A02细胞对阿霉素的耐药性有部分逆转作用(5.67倍),作用于K562/A02细胞后,细胞膜糖蛋白P170的表达从(85.3±5.5)%下调至(34.8±1.2)%,DNR外渗试验显示,细胞内化疗药物的质量浓度明显增加。结论:麻黄碱通过下调K562/A02细胞膜糖蛋白P170的表达,抑制其将化疗药物“泵”出细胞外的功能,提高化疗药物在K562/A02细胞内的有效质量浓度,能部分逆转K562/A02细胞的多药耐药性。

OBJECTIVE To investigate the effect and mechanism of ephedrine at non-cytotoxic concentration reversing the multidrug resistant （MDR） leukemia cell lines K562/A02. METHODS MTT colorimetry was used to determine the cytotoxic effect of ephedrine; FACS was used to determine the expressive and functional changes of glycoprotein-170 （P-170） on the cell membrane dealed with ephedrine at non-cytotoxic concentration. RESULTS Ephedrine had definite cytotoxic effect on K562/ A02,it＇s 10% inhibiting concentration（IC10） was 75 mg·L^-1, ephedrine at non-cytotoxic concentration could partly reverse MDR of K562/A02（5. 67 times）,and could descend the expression of P-170 from（85. 3 ± 5.5）% to（34. 8 ± 1.2）%. The exosmosis test of DNR showed that intracellular drug concentration increased evidently. CONCLUSION Via descending the expression of P-170 on K562/A02,ephedrine can restrain the function of pumping chemotherapeutics out of the cell, enhance the efficient intracellular concentration of chemotherapeutics, and partly reversed MDR of K562/A02.