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目的:探讨五味子甲素对表达多药耐药相关蛋白1的肿瘤耐药细胞株的逆转耐药作用及相关机制。方法:FCM测定不同浓度五味子甲素对柔红霉素抑制HL60/ADR生长及同一浓度五味子甲素对不同化疗药物抑制HL60/ADR和HL60/MRP细胞生长的影响;五味子甲素作用前后,HL60/ADR和HL60/MRP细胞内化疗药物柔红霉素和MRP1特异性底物二醋酸羧基荧光素积聚的变化。结果:25μmol/L五味子甲素可有效降低HL60/ADR、HL60/MRP对柔红霉素、长春新碱和依托泊甙的半数抑制浓度,逆转倍数分别是5,11,16和3,3,13倍;五味子甲素能够增加柔红霉素和MRP1特异性底物二醋酸羧基荧光素在细胞内的积聚。结论:五味子甲素可以逆转不同化疗药物对MRP1介导的耐药,其逆转机制与增加化疗药物的积聚能力有关。
Objective: To investigate the reversal drug resistance of schizandrin on the multidrug resistance-associated protein 1 (MDR-1) -resistant tumor cell lines and its related mechanisms. METHODS: FCM was used to determine the effect of different concentrations of Schisandra chinense on daunorubicin inhibition of HL60 / ADR growth and the same concentration of Schisandrins on the growth of HL60 / ADR and HL60 / MRP cells treated with different chemotherapeutic drugs. Before and after Schisandrin treatment, HL60 / ADR and HL60 / MRP intracellular chemotherapy drugs daunorubicin and MRP1 specific substrate carboxyfluorescein diacetate accumulation changes. Results: 25μmol / L deoxyschizandrin could effectively reduce the half inhibitory concentrations of daunorubicin, vincristine and etoposide by HL60 / ADR and HL60 / MRP respectively, and the fold of reversal was 5, 11, 16 and 3, 13 times; Schisandrin A can increase daunorubicin and MRP1-specific substrate carboxyfluorescein diacetate accumulation in the cell. Conclusion: Schisandrin can reverse the MRP1-mediated resistance of different chemotherapeutic drugs, and its reversal mechanism is related to the accumulation of chemotherapeutic drugs.