Establishment Of Multidrug Resistance Lung Adenocarcinoma Cell Line A549/ADM And Investigation Of The Reversal Of Drug Resistance By Azithromycin.

Objective To establish a multidrug-resistant cell line A549/ADM induced by azithromycin in vitro and investigate the reversal effect of azithromycin to A549/ADM. Methods A549 cells were treated with adriamycin (ADM). The cells were treated with low concentration of ADM firstly and then gradually increased concentration of ADM intermittently . The expressions of P-GP and MRP in A549 and A549/ADM were confirmed by flow cytometry(FCM). The 50% restrain concentration (IC₅₀) of four drugs to A549 and A549/ADM were evaluated with MTT assay. Same methods were used to A549/ADM when treated with azithromycin(AZM). The inhibition rates of different concentration of AZM to A549/ADM were also evaluated with MTT assay. The fluorescence intensity of ADM in A549 and A549/ADM with or without AZM added were also evaluated with FCM. Results The expressions of P-GP and MRP in A549 were 2.3% and 2.5% respectively, but those of A549/ADM were 33% and 46.3% respectively.The resistance index of A549/ADM to ADM was 17.80 times higher than that of A549 and the cells showed resistant to DDP, VCR and MTX incoordinately .With AZM added(5μg/ml), the sensitivities of A549/ADM to ADM were 2.81 times higher than before and sensitivities to DDP,VCR and MTX increased by 1.86, 3.78 and 3.86 times respectively. The sensitivities of A549/ADM to these drugs were much higher when treated with 10μg/ml of AZM. With the same treatment, the fluorescence intensities in A549 , A549/ADM and A549/ADM were 121.4, 51.2 and 96 respectively. Conclusions A549/ADM were multidrug- resistant(MDR) .The high expressions of P-GP and MRP might play an important role in MDR. AZM could reverse the MDR of A549/ADM through increase the accumulation of drugs in cells and the effection of reversal correlates with concentration.