Reversal of Multidrug Resistance of A549/DDP in Nude Mice by Arsenic Trioxide

Objective To study the reversing effect of arsenic trioxide(As_2O_3) on multidrug resistacne (MDR) of A549/DDP cell in vivo.Methods The transplantable lung carcinoma cell line A549/DDP model was developed in BALB/C mice by subcutaneous implantation.To observe the volume of tumor and detect the changes of P-gp expression and apoptosis rate after different drug treatment.RT-PCR assay was used to determine the expressive level of MRP1 and LRP-mRNA.Results As_2O_3 had some effect on inhibition of tumor growth combined with DDP could significantly inhibit tumor growth in BALB/C mice, the volume and weight of tumor which treated by As_2O_3 was lower than that in the control.0.25mg/kg As_2O_3 could effectively reverse the resistance of A549/DDP cell to DDP in vivo.FCM results showed that the expression of P-gp after using DDP was relatively higher than that using other drugs.The rate of apoptosis in groups in which arsenic trioxide treatment was used was significantly increased compared with that in both the control and the group DDP.RT-PCR was used to detect the MRP1-mRNA and LRP-mRNA. The expression of MRPl-mRNA was significantly higher in the groups in which As_2O_3 was used for treatment than that both in the control and the group DDP(P0.05).However,the expression of LRP-mRNA was same in the both groups(P0.05).Conclusion As_2O_3 can effectively reverse the resistance of A549/DDP cells in BALB/C to DDP and induce apoptosis of A549/DDP cells in vivo,which may complete by downregulating MRP1 gene expression,enhance the sensibility of A549/DDP to DDP and inducing the apoptosis of tumor cell.