Reversal Effect And Mechanism Of Elemene On Multidrug-resistant Of Human Osteosarcoma Cell Line (MG-63/ADM) In Vitro

Objective:To study the Reversal Effect and Mechanism of Elemene on Multidrug-resistant of human osteosarcoma cell line(MG-63/ADM)in vitro.Methods:To investigate the IC₅₀of adriamycin(ADM),IC₀₅and IC₁₅of elemene(ELE)to MG-63 human osteosarcoma cell by MTT assay. The MG-63 human osteosarcoma cell divide into three groups randomly (A,B,C Group).Group A is the control group,to establish a multi-drug resistant of human MG-63 cells by short-time pulse exposure of the cell to the IC₅₀of adriamycin.The cell of Group B,C are exposed both in the same dosage of ADM with the control group and IC₀₅(group B)or IC₁₅ (group C)of elemene.The exposure continued until the cell of Group A can be cultured stably in the nutritive medium which contain IC₅₀of ADM,then drug exposure are stopped in all experiment Groups.we repeat to investigate the IC₅₀of adriamycin to all post-drug intervention MG-63 human osteosarcoma cells by MTT assay.And intracellular accumulation of ADM were determined by fluorospectrophotometery.Flowcytometry was applied to study the MRP1 expression of initial and post-drug intervention MG-63 cells.At the end,we analyse the experimental result by statistics.Results:â‘ The IC₅₀of adriamycin(ADM)to MG-63 cells were 3.37μg/ml(GroupA),2.21μg/ml(GroupB),1.19μg/ml(GroupC),and the RF values were 11.62(GroupA),7.62(GroupB)and 4.10(GroupC),the comparisons among Group A,GroupB and Group C have statistical significance(P＜0.05).â‘¡The intracellular accumulation of ADM all experiment groups were 1.21μg/10⁶ cells(Group A),1.96μg/10⁶ cells(GroupB),2.71μg/10⁶ cells(Group C),Group A＜GroupB＜Group C,the comparisons among Group A,GroupB and Group C have statistical significance(P＜0.05).â‘¢the MRP1 expression rates of initial and post-drug intervention MG-63 cells were 10.38%(initial cells), 36.08%(Group A),25.30%(Group B)and 21.64%(Group C),the comparisons among Group A,GroupB and Group C have statistical significance(P＜0.05)Conclusion:firstly,we conclude that the multi-drug resistance to ADM of human osteosacoma eell(MG-63/ADM)could be reversed by Elemene with non-toxic or low-toxic dosage;Secondly the expression of multidrug resistance associated protein 1(MRP1)could be regulated down by Elemene;the last,the increased intracellular accumulation of ADM and downregulation of MRP1 would contribute to the reversal mechanism of Elemene.