摘要
Objective：We supposed that it will be a promising strategy to ＂prevent＂ multidrug resistance （MDR） instead of ＂reversing＂ it.This study was designed to investigate the potency of curcumin to prevent the acquired drug resistance induced by adriamycin （ADM） in native K562 cells.Methods：K562 cells were pretreated with curcumin or 0.5% DMSO for 24 h and then were co-incubated with ADM.P-glycoprotein （P-gp） and mdr1 mRNA levels were analyzed separately by flow cytometry and quantitative real-time RT-PCR.The intracellular Rh-123 accumulation was also detected by flow cytometer.Finally,we performed a MTT assay to determine the ADM-induced cytotoxicity with or without pretreatment of curcumin.Results：P-gp and mdr1 mRNA expressions were elevated in the ADM alone group.While in the curcumin pretreated groups,the induced P-gp and mdr1 mRNA levels gradually decreased with increasing curcumin concentrations,and the Rh-123 accumulation level was almost recovered close to the control group＇s.Finally,the MTT colorimetric assay verified the enhanced effect of curcumin on ADM-induced cytotoxicity.Conclusion：Our present study suggested that curcumin exhibits the novel ability to prevent the up-regulation of P-gp and its mRNA induced by ADM.The prevention capacity is also functionally associated with the elevated intracellular drug accumulation and parallel enhanced ADM cytotoxicity.We revealed a novel function of curcumin as a potential drug resistance preventor.
Objective：We supposed that it will be a promising strategy to ＂prevent＂ multidrug resistance （MDR） instead of ＂reversing＂ it.This study was designed to investigate the potency of curcumin to prevent the acquired drug resistance induced by adriamycin （ADM） in native K562 cells.Methods：K562 cells were pretreated with curcumin or 0.5% DMSO for 24 h and then were co-incubated with ADM.P-glycoprotein （P-gp） and mdr1 mRNA levels were analyzed separately by flow cytometry and quantitative real-time RT-PCR.The intracellular Rh-123 accumulation was also detected by flow cytometer.Finally,we performed a MTT assay to determine the ADM-induced cytotoxicity with or without pretreatment of curcumin.Results：P-gp and mdr1 mRNA expressions were elevated in the ADM alone group.While in the curcumin pretreated groups,the induced P-gp and mdr1 mRNA levels gradually decreased with increasing curcumin concentrations,and the Rh-123 accumulation level was almost recovered close to the control group＇s.Finally,the MTT colorimetric assay verified the enhanced effect of curcumin on ADM-induced cytotoxicity.Conclusion：Our present study suggested that curcumin exhibits the novel ability to prevent the up-regulation of P-gp and its mRNA induced by ADM.The prevention capacity is also functionally associated with the elevated intracellular drug accumulation and parallel enhanced ADM cytotoxicity.We revealed a novel function of curcumin as a potential drug resistance preventor.
基金
supported by the National Natural Science Foundation ofChina (No. 30901741)
Zhejiang Provincial Natural Science Foundation(No. Y2080308)
