摘要
目的:探讨欧白芷素对耐药细胞株K562/A02中P-糖蛋白(P-glycoprotein,P-gp)的影响,为抗白血病多药耐药(multi-drug resistance,MDR)提供新方法。方法:采用MTT法观察阿霉素对细胞活力的影响。应用流式细胞术检测欧白芷素对K562和K562/A02细胞内阿霉素累积和细胞中P-gp功能的影响。采用实时定量RT-PCR技术检测MDR1基因在mRNA表达水平的变化。结果:欧白芷素对耐药细胞株K562/A02有显著的逆转耐药活性,最大逆转倍数为7.36。在K562/A02细胞中,欧白芷素明显增加阿霉素的累积,增加了罗丹明123(rhodaminel123,Rh123)蓄积,抑制了Rh123的外排,同时欧白芷素还在mRNA水平抑制了K562/A02细胞中P-gp的表达。结论:欧白芷素能够抑制K562/A02耐药细胞株中MDR1基因表达和P-gp的功能。
AIM： To investigate the reversal effect of archangelicin （Arc） on multidrug resistance （MDR） in the doxorubicin （Dox）-resistant leukemic cell line K562/A02. METHODS： Cytotoxicity was assayed by 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide method; the DOX and Rh123 concentration in cells and the expression of P-glycoprotein were assayed by flow cytometry. The influence of Arc on P-gp expression at mRNA levels was determined by using real-time RT-PCR. RESULTS： Arc was endowed with remarkable MDR-reversing effect in K562/A02, and the maximal reversal fold （RF） was 7.36. The action of Arc was confirmed by the increase of intracellular accumulation of Dox in K562/A02 cells. The function of P-gp was blocked, and the expression of MDR1 mRNA and P-gp were inhibited by Arc. CONCLUSION： Arc reversed effectively MDR via inhibiting P-gp expression and function, and may be used as MDR reversal drugs to increase the effectiveness of chemotherapy.
出处
《中国天然药物》
SCIE
CAS
CSCD
北大核心
2011年第2期146-150,共5页
基金
supported by the Natural Science Foundation of Shandong Province (No.Y2008C98)~~
