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AIM: To investigate the effect of MRP1 shRNA on apoptosis and drug sensitization in cisplatin-resistance human lung cancer cell line A549/DDP and to determine the inhibitory effect of the MRP1 shRNA on the expression ofMRP1 gene in cells A549/DDP.METHODS: MRP1 shRNA and negative shRNA plasmid vector were instantaneously transfected into A549/DDP cells.Drug sensitivity of the cells to cisplatin (DDP) was analyzed with MTT and flow cytometry.RT-PCR and Western blot were used to detect the target gene expression.RESULTS: MTT results showed that MRP1 shRNA transfectants had a higher cell inhibition rate than negative shRNA or untreated cells after treated with 10、 20、 40、 80、 160umol/L DDP.Moreover, flow cytometry results demonstrated that MRP1 shRNA cells had increased apoptosis rate after addition of 40 umol/L DDP.Spontaneous apoptosis of cells were significantly increased in MRP1 shRNA instantaneously transfectants.The mRNA and protein expression level of MRP 1 in MRP 1 shRNA instantaneously transfectants were obviously reduced compared with negative shRNA transfectants or untreated cells.CONCLUSION: shRNA targeting MRP1 gene can specifically down-regulate MRP1 expression in A549/DDP cells, increase cell spontaneous apoptosis and sensitize cells to DDP.MRP1 shRNA may be a potential therapy agent against human lung cancer.