Establishment Of Multidrug-resistant Lung Adenocarcinoma Cell Lines A549/ADM And Reversal Of Drug-resistance

Objective To study the mechanisms of multidrug resistance in lung adenocarcinoma cell line A₅₄₉/ADM and found the effect reversal of multidrug resistance . Methods: By culturing with continous and intermittent gradual increasing-concentration of ADM, a human lung adenocarcinoma multidrug-resistant cell line- A₅₄₉/ADM was established. The expressions of resistance proteins MRP and P-gp and the accumulation of ADM in A₅₄₉/ADM cells were detected with flow cytometry. The resistance to chemotherapeutic drugs and the reversal with levofloxacin were valuated with MTT way. Results A₅₄₉/ADMcells were proved multidrug-resistant . The resistance index of A₅₄₉/ADM to ADM, DDP, VCR and VP16 was 11.76,3.06,20.64 and5.38 respectively, but not to 5-FU; Compared with A₅₄₉ cells,the expressions of P-gp and MRP rise up to 33.4% and 46.8% respectively. With levofloxacin (40μg/ml) added sensitivity of A₅₄₉/ADM cells to ADM raised by 11.92 times and accumulation of ADM in A₅₄₉/ADM cells was significantly, increased Sensitivity to VCR and VP16 increased by 5.54, 5.91 times respecitively.but to DDP no effect. Conclusions A₅₄₉/ADM cells were resistant to clinically common used anti-cancer chemotherapeutic drugs and the resistance might related to P-gp and MRP overexpression.. levofloxacin is most likely effective MRP biological response modifier in vitro. It could partly reverse the MDR of lung adenocarcinoma cell lines...